Science.gov

Sample records for orthotopic neobladder replacement

  1. Orthotopic neobladder reconstruction

    PubMed Central

    Chang, Dwayne T. S.; Lawrentschuk, Nathan

    2015-01-01

    Orthotopic neobladder reconstruction is becoming an increasingly common urinary diversion following cystectomy for bladder cancer. This is in recognition of the potential benefits of neobladder surgery over creation of an ileal conduit related to quality of life (QoL), such as avoiding the need to form a stoma with its cosmetic, psychological and other potential complications. The PubMed database was searched using relevant search terms for articles published electronically between January 1994 and April 2014. Full-text articles in English or with English translation were assessed for relevance to the topic before being included in the review. Patients with neobladders have comparable or better post-operative sexual function than those with ileal conduits. They also have comparable QoL to those with ileal conduits. Orthotopic neobladder is a good alternative to ileal conduit in suitable patients who do not want a stoma and are motivated to comply with neobladder training. However, the selection of a neobladder as the urinary diversion of choice requires that patients have good renal and liver functions and are likely to be compliant with neobladder training. With benefits also come potential risks of neobladder formation. These include electrolyte abnormalities and nocturnal incontinence. This short review highlights current aspects of neobladder formation and its potential advantages. PMID:25657535

  2. Intravesical OnabotulinumtoxinA Injection for Overactive Orthotopic Ileal Neobladder: Feasibility and Efficacy

    PubMed Central

    2016-01-01

    The efficacy of intravesical onabotulinumtoxinA (BTXA) in the treatment of overactive bladder (OAB) has been well documented. The use of BTXA injection in orthotopic neobladders is yet to be studied. We present 4 cases of patients injected with intravesical BTXA for overactive orthotopic ileal neobladder. We recorded patient demographics, presenting and follow-up symptoms, urodynamic profiles, and Patient Global Impression of Improvement (PGI-I) scores. The 4 patients reported varying degrees of subjective improvements in the symptoms, including urgency, urge incontinence, and pad usage. Mean follow-up duration was 8.3 months (range, 5–14 months). Average PGI-I score was 3 (“a little better”) (range, 2–4). To our knowledge, the current study is the first case series examining BTXA injection for orthotopic neobladder overactivity. BTXA injection yielded varying degrees of objective and subjective improvements, without significant complications. Intravesical BTXA injection is feasible and may be considered as a potential treatment alternative for OAB in orthotopic neobladders, although further study is warranted. PMID:27032562

  3. Comparison Between Ambulatory and Conventional Urodynamics of the Modified Orthotopic Hautmann Neobladder

    PubMed Central

    Georgios, Dimitriadis; Georgios, Gkotsos; Ioannis, Vakalopoulos; Stavros, Ioannidis; Konstantinos, Hatzimoutatidis; Dimitrios, Hatzichristou

    2015-01-01

    Purpose: The aim of the present study was to determine the diagnostic accuracy of conventional and ambulatory urodynamic studies (UDS) in estimating neobladder function. Methods: We evaluated 32 patients who underwent radical cystectomy and orthotopic Hautmann W neobladder with Abol-Enein-Ghoneim uretero-intestinal anastomosis for bladder cancer. The patients were initially examined by using both conventional and ambulatory UDS. Results: Conventional UDS detected a very high mean intravesical pressure at maximum capacity (53.7±17.5 cm H2O). By contrast, the mean intravesical pressure detected by using ambulatory UDS (which reflects the dominant pattern of pressure variation during filling) was significantly lower (34.4±5.2 cm H2O, P<0.001). The comparison between intravesical pressure at half of maximum capacity in conventional UDS and the mean value in ambulatory UDS did not show significant difference (P=0.152). The mean voided volume in conventional UDS was greater than both the mean voided volume (P<0.001) and the mean maximum voided volume in ambulatory UDS (P=0.001). However, this difference did not affect the postvoid residual urine volume measured in both studies (P=0.207). Moreover, incontinence episodes recorded in ambulatory UDS were more frequent but not statistically significantly different from those recorded in conventional UDS (P=0.332). Conclusions: The estimation of neobladder function by means of ambulatory UDS seems to provide interesting research data for the mode of lower urinary tract function in patients with orthotopic substitution after radical cystectomy. The great high value in ambulatory UDS, in cases in which conventional UDS had failed, is due to the exposure of daily and nocturnal incontinence episodes, confirming our patients’ complaints. PMID:26739181

  4. [Technique of the urethral anastomosis in orthotopic neo-bladder following robot-assisted radical cystectomy (RARC)].

    PubMed

    Horstmann, M; Kurz, M; Padevit, C; Horton, K; John, H

    2013-03-01

    The urethral anastomosis in extracorporeally constructed orthotopic neo-bladder following robot-assisted radical cystectomy (RARC) remains a challenge. In principle either pre-posi-tioned single sutures or robotic continuous suture techniques can be applied. In the literature the different techniques are most often not described in detail. In the present work one example for each technique is given and the advantages and disadvantages of both methods are discussed.

  5. Preperitoneal placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction after radical cystoprostatectomy with orthotopic neobladder

    PubMed Central

    Kim, Jung Kwon; Cho, Min Chul; Ku, Ja Hyeon

    2016-01-01

    Purpose To describe a case of safe placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction (ED) with a history of radical cystoprostatectomy with an orthotopic Studer neobladder. Materials and Methods A 55-year-old bladder cancer patient, who underwent radical cystoprostatectomy with orthotopic Studer neobladder 2 years prior, suffered from postoperative ED. A 3-piece inflatable penile prosthesis was implanted via a penoscrotal incision. The alternative reservoir placement began with a longitudinal 4-cm incision, which was 2 finger-breaths to the left and lateral to the umbilicus. Thereafter, the anterior and posterior rectus sheaths were dissected and incised. Then, the transversalis fascia entering into the preperitoneal space was incised, followed by circumferential sweeping using the forefinger, and, finally, placement of a 100 mL 'flat' reservoir. The reservoir was filled with 65 mL saline and then evaluated for back pressure. The reservoir tubing exited through the defect of the rectus sheaths and tunneled through the abdominal fat into the penoscrotal wound. Results Total operative time was 105 minutes, and the estimated blood loss was minimal. The patient was discharged at postoperative day 1 and experienced no perioperative complications. At the 6-month follow-up, there was no abdominal bulging from the preperitoneal reservoir, and the reservoir was not palpable. Conclusions The preperitoneal placement of the flat reservoir at the level of the umbilicus is a safe and acceptable surgical technique for postoperative ED after radical cystoprostatectomy with orthotopic neobladder.

  6. Preperitoneal placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction after radical cystoprostatectomy with orthotopic neobladder

    PubMed Central

    Kim, Jung Kwon; Cho, Min Chul; Ku, Ja Hyeon

    2016-01-01

    Purpose To describe a case of safe placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction (ED) with a history of radical cystoprostatectomy with an orthotopic Studer neobladder. Materials and Methods A 55-year-old bladder cancer patient, who underwent radical cystoprostatectomy with orthotopic Studer neobladder 2 years prior, suffered from postoperative ED. A 3-piece inflatable penile prosthesis was implanted via a penoscrotal incision. The alternative reservoir placement began with a longitudinal 4-cm incision, which was 2 finger-breaths to the left and lateral to the umbilicus. Thereafter, the anterior and posterior rectus sheaths were dissected and incised. Then, the transversalis fascia entering into the preperitoneal space was incised, followed by circumferential sweeping using the forefinger, and, finally, placement of a 100 mL 'flat' reservoir. The reservoir was filled with 65 mL saline and then evaluated for back pressure. The reservoir tubing exited through the defect of the rectus sheaths and tunneled through the abdominal fat into the penoscrotal wound. Results Total operative time was 105 minutes, and the estimated blood loss was minimal. The patient was discharged at postoperative day 1 and experienced no perioperative complications. At the 6-month follow-up, there was no abdominal bulging from the preperitoneal reservoir, and the reservoir was not palpable. Conclusions The preperitoneal placement of the flat reservoir at the level of the umbilicus is a safe and acceptable surgical technique for postoperative ED after radical cystoprostatectomy with orthotopic neobladder. PMID:27617319

  7. Cystectomy with orthotopic ileal neobladder reconstruction for treatment of bladder contracture after intravesical bacillus Calmette-Guerin therapy

    PubMed Central

    Vetorazzo, José Eduardo; Bahia, Leandro Augusto Costa; Vedovato, Bruno César; Maron, Paulo Eduardo Goulart; Esteves, Paulo Ebert; Fernandes, Roni de Carvalho; Perez, Marjo Deninson Cardenuto

    2014-01-01

    Bladder cancer is an important health problem worldwide due to high prevalence rates and costs related to treatment. A reduction in recurrence rates has been observed since the introduction of adjuvant intravesical immunotherapy with bacillus Calmette-Guerin. There are mild complications that are easily solved by local measures and orientations. Bladder contracture, a rare and severe local complication, in some cases leading to disability, is observed primarily in patients in a maintenance program. In this article we reported the case of a male patient who underwent transurethral resection of the bladder because of a high-grade T1 urothelial carcinoma and developed this complication during treatment with bacillus Calmette-Guerin. For this reason he was submitted to cystoprostatectomy with orthotopic ileal neobladder reconstruction. PMID:25628205

  8. The ileal neobladder--updated experience with 306 patients.

    PubMed

    Flohr, P; Hefty, R; Paiss, T; Hautmann, R

    1996-01-01

    From April 1986 through May 1995, 306 men with primary urothelial carcinoma underwent radical cystoprostatectomy and orthotopic bladder substitution via the ileal neobladder. Altogether, 7.5% of the patients suffered general early complications, including thrombosis, embolism, wound infection, and pneumonia. Specific early complications directly related to formation of the neobladder and requiring surgery included ileus (4%), abscess drainage (2%), and leakage of the ileal anastomosis (0.5%). The early reoperation rate was 6.5%. Early complications that required temporary percutaneous drainage were lymphocele formation (3%) or ureteral obstruction (6%). In all, 9% of our patients required prolonged catheter drainage for leakage of the ileouretheral anastomosis. Late complications requiring reoperation were ileus (2%), abscess drainage (1%), neobladder fistula to the colon (1.5%), ureteral reimplantation because of obstruction (3.6%), and nephrectomy for hydronephrosis (1%). A transurethral incision of the ileouretheral anastomosis was necessary in 7% of cases. Continence was separately addressed by sending each patient and his home physician a detailed questionnaire: Using our criteria (no diapers, no awakenings) the night and day continence rate increased from 67% at 6 months, to 72% at 1 year to 85% at 2 years, finally reacting 90% after 4 years. In part II of this presentation we address the question as to whether the option of orthotopic bladder replacement has any impact on the patient's and physician's decision toward earlier cystectomy. We compared our ileal neobladder cohort with a group of 137 patients that had been operated on during the same time span by the same group of surgeons. There was no negative selection with regard of the tumor stage of our patients. However, as compared with the conduit group, the neobladder cohort had a significantly improved survival rate. This phenomenon is explainable by the significantly lower number of previous

  9. Successful Management of Neobladder Variceal Bleeding.

    PubMed

    Atwal, Dinesh; Chatterjee, Kshitij; Osborne, Scott; Kakkera, Krishna; Deas, Steven; Li, Ruizong; Erbland, Marcia

    2016-10-01

    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.

  10. Neobladders: clinical management and considerations for patients receiving chemotherapy.

    PubMed

    Broderick, G A; Stone, A R; deVere White, R

    1990-10-01

    Continent catheterizable urinary reservoirs and orthotopic bladder substitutes are complex surgical endeavors. The goal is preservation of renal function, reliable continence, and storage intervals acceptable to the patient. The construction requires familiarity with bowel segments and may increase operative time for radical cystoprostatectomy by 30% to 50%. Patients with continent reservoirs have improved body image, work habits, and sexual and interpersonal relationships. Experience with patients with dysfunctional neurogenic bladders previously converted to Bricker urostomies now undiverted to continent reservoirs indicates an overall increase in physical activity and self-satisfaction. These patients are tolerant of reoperations to maintain independence from wet urostomies. Undoubtedly, the expectations of bladder cancer patients will differ from those of young adults with neurogenic bladder, but we have found that when all options are presented patients will seek out therapy that least alters their body image. Therefore, patient selection becomes an important factor in determining the success of continent reservoirs. Patients must have the dexterity and motivation to catheterize the urinary reservoir, irrigate for mucus and, in cases of orthotopic bladder replacement to urethra, accept the need for artificial sphincter placement in 30% to 40% of cases. Management of the neo-bladders requires additional consideration of several practical and theoretic points for both the surgeon and medical oncologist: 1. Patients with diffuse carcinoma in situ or transitional cell carcinoma at the bladder neck or prostatic urethra should undergo simultaneous urethrectomy excluding orthotopic bladder replacement. 2. Ten percent to 40% of patients undergoing radical cystoprostatectomy for transitional cell cancer will have concomitant underdiagnosed adenocarcinoma of the prostate; patient prognosis will remain defined by the stage and grade of the bladder cancer. 3. Patients may

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

    PubMed Central

    2016-01-01

    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. PMID:27366009

  12. Discussion on robot-assisted laparoscopic cystectomy and Ileal neobladder surgery preoperative care.

    PubMed

    Zhang, Daoxiu; Su, Mingyang; Liu, Chunlei; Zhao, Huiping

    2016-01-01

    To investigate the clinical applications of robot-assisted radical cystectomy with orthotopic ileal neobladder (RARC-INB) and make a preliminary summary. Retrospective analysis the clinical data of 12 patients underwent robotic bladder cancer (da vinci surgical system) assisted laparoscopic cystectomy with ileal orthotopic neobladder from March 2015 to April 2015. 12 cases were successful, with no surgical intervention, and organ damage occurred. The operation time was 330~470 min, which average (390.0±61.5) min; blood loss was 90~870 ml, which average (185.0±88.3) ml. One case of intraoperative blood transfusion was 400 ml. The enjoin eating time of postoperative intestinal ventilation was 3~6 d, and the average time was (4.0±1.5) d. Removal of ureteral stents time was 14~28 d and the average time was (21±7) d. Removal of the catheter time was 18~28 d and the average time was (23±5) d. Postoperative hospital stay 19~29 d and the average time was (24±5) dRARC-INB make the surgical tends to simplify, which was conducive to surgeon intraoperative control and assurance. RARC-INB make the surgical tends to use less trauma, less bleeding, complete lymphadenectomy, quick recovery, etc. It is a safe, effective and reliablethe method in the treatment of invasive bladder cancer. So the method should be widely applied. PMID:27005509

  13. Radical Cystectomy and Orthotopic Bladder Substitution Using Ileum

    PubMed Central

    Park, Jinsung

    2011-01-01

    Over the past decade, continent urinary diversion, especially orthotopic bladder substitutions, has become increasingly popular following radical cystectomy for bladder cancer. The ultimate goal of orthotopic bladder substitution is to offer patients the best quality of life, similar to that of patients with native bladders. To achieve that purpose, surgeons should be familiar with the characteristics of good candidates for neobladders, the possible intraoperative and postoperative problems related to the surgery, and the solutions to these problems. Postoperative surveillance and instructions given to the patients also contribute to successful, functional results. Here, we reviewed the indications, pitfalls, and solutions for orthotopic bladder substitutions and the patients' quality of life after surgery. When performed properly, orthotopic continent diversion offers good quality of life with few long-term complications. Therefore, we believe it is the best option for the majority of patients requiring cystectomy. PMID:21556208

  14. Medial thigh pain: An unusual presentation of giant calculi in sigmoid neobladder

    PubMed Central

    Abrol, Nitin; Gupta, Narmada; Kumar, Rajeev

    2011-01-01

    Calculi in a neobladder usually present with irritative lower urinary tract symptoms, flank pain, and haematuria. We report a case of giant stones in a sigmoid neobladder, who presented with medial thigh pain. PMID:21814323

  15. Diagnosing spontaneous ileal neobladder perforation: Too often delayed.

    PubMed

    Rosenberg, Shilo; Gofrit, Ofer N; Hidas, Guy; Landau, Ezekiel H; Pode, Dov

    2013-01-01

    Spontaneous neobladder perforations are rare, but well-documented; the first cases were reported more than 2 decades ago mostly in urologic journals. However, the diagnosis of these patients is often delayed in the emergency room setting because initial care is given by non-urological medical staff that is too often unaware of this etiology. We present 2 cases and discuss the shift in treatment that has occurred over time. PMID:24475003

  16. Sacrocolpopexy with Polypropylene Tape as Valuable Surgical Modification during Cystectomy with Orthotopic Ileal Bladder: Functional Results

    PubMed Central

    Życzkowski, Marcin; Kaletka, Zbigniew; Bryniarski, Piotr; Paradysz, Andrzej

    2015-01-01

    Introduction. Urinary diversion is very often associated with urinary retention and urinary incontinence. In this study, a surgical modification during cystectomy with orthotopic ileal neobladder is presented. Material and Methods. Female patients enrolled in the study (n-24) were subjected to sacrocolpopexy during the operation. Apart from oncological control, the follow-up consisted of 1-hour inlay test and questionnaires (UDI-6 and IIQ-7) in the 3rd, 6th, and 12th month after the operation. In the 12th month after the surgery, the urodynamic pressure-flow test was performed. Outcomes were compared with the control group (n-18) in which sacrocolpopexy was not implemented. Results. The study group was characterised by reduced urinary retention and improved continence. Conclusion. Sacrocolpopexy during cystectomy with orthotopic ileal bladder is a valuable surgical method which provides patients with a better quality of life. PMID:25789311

  17. Sacrocolpopexy with polypropylene tape as valuable surgical modification during cystectomy with orthotopic ileal bladder: functional results.

    PubMed

    Życzkowski, Marcin; Muskała, Bartosz; Kaletka, Zbigniew; Bryniarski, Piotr; Nowakowski, Krzysztof; Bogacki, Rafał; Paradysz, Andrzej

    2015-01-01

    Introduction. Urinary diversion is very often associated with urinary retention and urinary incontinence. In this study, a surgical modification during cystectomy with orthotopic ileal neobladder is presented. Material and Methods. Female patients enrolled in the study (n-24) were subjected to sacrocolpopexy during the operation. Apart from oncological control, the follow-up consisted of 1-hour inlay test and questionnaires (UDI-6 and IIQ-7) in the 3rd, 6th, and 12th month after the operation. In the 12th month after the surgery, the urodynamic pressure-flow test was performed. Outcomes were compared with the control group (n-18) in which sacrocolpopexy was not implemented. Results. The study group was characterised by reduced urinary retention and improved continence. Conclusion. Sacrocolpopexy during cystectomy with orthotopic ileal bladder is a valuable surgical method which provides patients with a better quality of life.

  18. Transfemoral Transcatheter Aortic Valve Replacement for Mixed Aortic Valve Disease in Child's Class C Liver Disease Prior to Orthotopic Liver Transplantation: A Case Report.

    PubMed

    Wilkey, Barbara J; Hanson, Ross; Reece, T Brett; Forman, Lisa; Burton, James R; Messenger, John C; Kim, Michael S; Cleveland, Joseph C; Fiegel, Matt J; Nydam, Trevor L; Mandell, M Susan

    2016-06-01

    The American Association for the Study of Liver Diseases practice guidelines list severe cardiac disease as a contraindication to liver transplantation. Transcatheter aortic valve replacement has been shown to decrease all-cause mortality in patients with severe aortic stenosis who are not considered candidates for surgical aortic valve replacement. We report our experience of liver transplantation in a patient with severe aortic stenosis and moderate aortic insufficiency who underwent transcatheter aortic valve replacement with Child-Pugh Class C disease at a Model For End-Stage Liver Disease score of 29. The patient had a difficult post procedure course that was successfully medically managed. After liver transplantation the patient was discharged to home on postoperative day 11. The combination of cardiac disease and end stage liver disease is challenging but these patients can have a successful outcome despite very severe illness.

  19. The effect of N-acetyl-L-cysteine on the viscosity of ileal neobladder mucus.

    PubMed

    Schrier, B P; Lichtendonk, W J; Witjes, J A

    2002-05-01

    N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a refrigerator. After precipitation, the urine was decanted. The residue was stirred to a homogeneous suspension. To samples of 4.5 ml mucus, 0.5 ml NAC 10% was added. To the control sample, 0.5 ml water was added. The samples were incubated in a water bath at 37 degrees C for 5, 30 and 60 min. Viscosity was measured in the Bohlin VOR Rheometer. The viscosity of the ileal neobladder mucus decreased quickly after incubating with NAC 10%. Viscosity increased slightly after I h of incubation. The viscosity in the control sample was higher than in the other incubated samples. NAC was found to decrease the viscosity of ileal neobladder mucus, supporting the in vivo experience that NAC can be useful in patients with an ileal neobladder to facilitate the evacuation of mucus by decreasing viscosity. PMID:12088194

  20. The effect of N-acetyl-L-cysteine on the viscosity of ileal neobladder mucus.

    PubMed

    Schrier, B P; Lichtendonk, W J; Witjes, J A

    2002-05-01

    N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a refrigerator. After precipitation, the urine was decanted. The residue was stirred to a homogeneous suspension. To samples of 4.5 ml mucus, 0.5 ml NAC 10% was added. To the control sample, 0.5 ml water was added. The samples were incubated in a water bath at 37 degrees C for 5, 30 and 60 min. Viscosity was measured in the Bohlin VOR Rheometer. The viscosity of the ileal neobladder mucus decreased quickly after incubating with NAC 10%. Viscosity increased slightly after I h of incubation. The viscosity in the control sample was higher than in the other incubated samples. NAC was found to decrease the viscosity of ileal neobladder mucus, supporting the in vivo experience that NAC can be useful in patients with an ileal neobladder to facilitate the evacuation of mucus by decreasing viscosity.

  1. Comparison of postoperative acute kidney injury between ileal conduit and neobladder urinary diversions after radical cystectomy

    PubMed Central

    Joung, Kyoung-Woon; Kong, Yu-Gyeong; Yoon, Syn-Hae; Kim, Yeon Ju; Hwang, Jai-Hyun; Hong, Bumsik; Kim, Young-Kug

    2016-01-01

    Abstract Ileal conduit and neobladder urinary diversions are frequently performed after radical cystectomy. However, complications after radical cystectomy may be different according to the type of urinary diversion. Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. This study was performed to compare the incidence of postoperative AKI between ileal conduit and neobladder urinary diversions after radical cystectomy. All consecutive patients who underwent radical cystectomy in 2004 to 2014 in a single tertiary care center were identified. The patients were divided into the ileal conduit and ileal neobladder groups. Preoperative variables, including demographics, cancer-related data and laboratory values, as well as intraoperative data and postoperative outcomes, including AKI, intensive care unit admission rate, and the duration of hospital stay, were evaluated between the groups. Postoperative AKI was defined according to the Kidney Disease: Improving Global Outcome criteria. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences. After performing 1:1 propensity score matching, the ileal conduit and ileal neobladder groups each included 101 patients. The overall incidence of AKI after radical cystectomy was 30.7% (62 out of 202) and the incidences did not significantly differ between the groups (27 [26.7%], ileal conduit group vs 35 [34.7%], ileal neobladder group, P = 0.268). Intraoperative data, intensive care unit admission rate, and the duration of hospital stay were not significantly different between the groups. Postoperative AKI did not significantly differ between ileal conduit and neobladder urinary diversions after radical cystectomy. This finding provides additional information useful for appropriate selection of the urinary diversion type in conjunction with radical cystectomy

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

    PubMed Central

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

    2014-01-01

    Introduction: The aim of this report is to describe our surgical technique of totally intracorporeal robotic assisted radical cystectomy (RARC) with neobladder formation. Materials and Methods: 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. Results: 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. Conclusions: Our experience with totally intracorporeal RARC demonstrates acceptable oncological and functional outcomes that suggest this is a viable alternative to open radical cystectomy. PMID:25097318

  3. Mitomycin-C suppresses mucus secretion in an ileal neobladder rat model

    PubMed Central

    FAN, WEIWEI; YU, YANG; SHU, JUNJIE; MING, HAO; LI, WEIPING; FAN, ZHILU

    2015-01-01

    The aim of the present study was to investigate the mucus secretion status of mature goblet cells following the application of mitomycin-C (MMC) in ileal neobladder rat models. Bladder substitution models were established in Sprague Dawley rats, which had been divided into five groups, namely the control (sham), normal saline (NS), high-dose MMC (HMMC), low-dose MMC (LMMC) and dehydrated alcohol (DA) groups. To evaluate the total protein concentration and level of sialic acid following the therapy, urine from the rats in each group was collected on days 8, 11 and 14. In addition, to observe the variances between mucus secretion and the ileum goblet cells, immunohistochemistry and hematoxylin and eosin staining were conducted in the different groups on day 17. The results indicated that the ileal neobladder mucosas in the MMC groups were clearly undamaged, as compared with the DA group. Furthermore, the MMC and DA groups were shown to inhibit the proliferation of goblet cells. The concentration of protein and sialic acid in the LMMC group was found to be lower compared with the NS group, while the concentration in the HMMC group was considerably lower. In conclusion, HMMC was demonstrated to evidently reduce the mucin and sialic acid concentration in the urine, without visible damage to the ileal neobladder mucus membrane. Therefore, MMC may provide a novel therapeutic approach for the treatment of certain bladder conditions. PMID:26622360

  4. Risk Factors for Developing Metabolic Acidosis after Radical Cystectomy and Ileal Neobladder

    PubMed Central

    Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Ryu, Dong-Ryeol; Lee, Dong Hyeon

    2016-01-01

    Purpose To investigate the serial changes of metabolic acidosis and identify associated risk factors in patients who underwent radical cystectomy and ileal neobladder. Material and Methods From January 2010 to August 2014, 123 patients who underwent radical cystectomy and ileal neobladder reconstruction for bladder cancer were included in this study. Metabolic acidosis was defined as a serum bicarbonate level less than 22 mEq/L and impaired renal function was defined as a GFR <50ml/min. The presence of metabolic acidosis was evaluated at 1 month, 1 year, and 2 years after surgery. Multivariate logistic regression analysis was conducted to identify risk factors associated with development of metabolic acidosis. Results Metabolic acidosis was observed in 52%, 19.5%, and 7.3% of patients at 1 month, 1 year, and 2 years after surgery, respectively. At 1 month after surgery, impaired renal function was the only independent risk factor associated with metabolic acidosis (OR 3.87, P = 0.046). At 1 year after surgery, diabetes was the only independent risk factor associated with metabolic acidosis (OR 5.68, P = 0.002). At 2 years post-surgery, both age and diabetes were significant risk factors associated with metabolic acidosis. Conclusion Approximately, half of patients experienced metabolic acidosis one month after ileal neobladder reconstruction. Preoperative impaired renal function was the most significant risk factor for developing metabolic acidosis in the early postoperative period. However, the incidence of metabolic acidosis decreased to less than 20% 1 year after surgery, and diabetes was an independent risk factor during this period. PMID:27384686

  5. Orthotopic urinary diversion after radical cystectomy in treatment of muscle invasive bladder cancer.

    PubMed

    Jovan, Hadži-Djokić; Vladan, Andrejević; Tomislav, Pejčić; Miodrag, Aćimović; Uroš, Babić; Miodrag, Stanić; Zoran, Džamić

    2014-01-01

    Surgical treatment of invasive carcinoma of the bladder in males includes total cystectomy removal of the prostate, seminal vesicles, and the distal parts of the urethers and the pelvic lymph node dissection as well. At this moment it is not possible to recommend a particular type of urinary diversion, but today in clinical practice commonly used derivative are ileal orthotopic neobladder as the continent one and ileal conduit as non-continent urinary diversion. Continent urinary diversion after radical cystectomy are the result of the application of technological innovation in surgery, but also knowledge, imagination and skill of well trained urologist. This type of operation significantly improves the quality of life in patients who underwent radical cystectomy, and the proposal is to operate whenever there is a possibility for this type of procedure. Also it is very important, during surgery to respect oncological principles, of complete removal of tumorous tissue and that the functional principle of ensur- ing that the patients have daytime and also nighttime continence later on after the surgery.

  6. Infections Following Orthotopic Liver Transplantation

    PubMed Central

    Arnow, Paul M.

    1991-01-01

    The epidemiology of infections associated with orthotopic liver transplantation is summarized herein, and approaches to prophylaxis are outlined. Infection is a major complication following orthotopic liver transplantation, and more than half of transplant recipients develop at least one infection. The risk of infection is highest in the first month after transplantation, and the most common pathogens are bacteria and cytomegalovirus (CMV). Bacterial infections usually occur in the first month, arise in the abdomen, and are caused by aerobes. The peak incidence of CMV infection is late in the first month and early in the second month after transplantationn. CMV syndromes include fever and neutropenia, hepatitis, pneumonitis, gut ulceration, and disseminated infection. Other significant problems are Candida intraabdominal infection, Herpes simplex mucocutaneous infection or hepatitis, adenovirus hepatitis, and Pneumocystis carinii pneumonia. Prophylaxis of infection in liver transplant recipients has not been well-studied. Several different regimens of parenteral, oral absorbable, and/or oral non-absorbable antibiotics active against bacteria and yeast have been used at various centers, but no randomized controlled trials have been conducted. Selective bowel decontamination appears to be a promising approach to the prevention of bacterial and Candida infections, while oral acyclovir may be a relatively convenient and effective agent for CMV prophylaxis. PMID:1650245

  7. A history of orthotopic heart transplantation.

    PubMed

    Meine, Trip J; Russell, Stuart D

    2005-01-01

    Orthotopic human heart transplantation today is performed at more than 150 U.S. centers, and the average survival is more than 10 years. Its prevalence and success, however, belies the fact that just 40 years ago, no one had ever attempted the procedure in humans and that the procedure seemed destined for failure just a year after the first transplant. This article reviews the history of orthotopic heart transplantation, beginning with ancient Greek legends and culminating in modern successes.

  8. Comparison of postoperative acute kidney injury between ileal conduit and neobladder urinary diversions after radical cystectomy: A propensity score matching analysis.

    PubMed

    Joung, Kyoung-Woon; Kong, Yu-Gyeong; Yoon, Syn-Hae; Kim, Yeon Ju; Hwang, Jai-Hyun; Hong, Bumsik; Kim, Young-Kug

    2016-09-01

    Ileal conduit and neobladder urinary diversions are frequently performed after radical cystectomy. However, complications after radical cystectomy may be different according to the type of urinary diversion. Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. This study was performed to compare the incidence of postoperative AKI between ileal conduit and neobladder urinary diversions after radical cystectomy.All consecutive patients who underwent radical cystectomy in 2004 to 2014 in a single tertiary care center were identified. The patients were divided into the ileal conduit and ileal neobladder groups. Preoperative variables, including demographics, cancer-related data and laboratory values, as well as intraoperative data and postoperative outcomes, including AKI, intensive care unit admission rate, and the duration of hospital stay, were evaluated between the groups. Postoperative AKI was defined according to the Kidney Disease: Improving Global Outcome criteria. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences.After performing 1:1 propensity score matching, the ileal conduit and ileal neobladder groups each included 101 patients. The overall incidence of AKI after radical cystectomy was 30.7% (62 out of 202) and the incidences did not significantly differ between the groups (27 [26.7%], ileal conduit group vs 35 [34.7%], ileal neobladder group, P = 0.268). Intraoperative data, intensive care unit admission rate, and the duration of hospital stay were not significantly different between the groups.Postoperative AKI did not significantly differ between ileal conduit and neobladder urinary diversions after radical cystectomy. This finding provides additional information useful for appropriate selection of the urinary diversion type in conjunction with radical cystectomy. PMID:27603401

  9. Survival up to 5–15 years in young women following genital sparing radical cystectomy and neobladder: oncological outcome and quality of life. Single–surgeon and single–institution experience

    PubMed Central

    Elganozoury, Hossam

    2015-01-01

    Introduction This is an observational retrospective study utilising long term patient follow–up for 15 years to determine the survival and quality of life in women (age range 20–54 years) after having been treated for carcinoma of the bladder by radical cystectomy with preservation of genital organs. Material and methods The study included 13 female patients with urothelial carcinoma of the bladder treated with genital sparing radical cystectomy during the period of 1995 until 2006. They had orthotopic ileal neobladder. Follow–up included recurrence–free survival, metastases–free survival, overall survival, continence, and sexual function. Results Genital sparing cystectomy was done in 13 women. Seven women were between the ages of 20–37, and 6 women were aged 38–54. Overall survival of 10–15 years was 61.53%, survival from 5 to 9 years was 38.46%. The procedure was done in 9 women with a muscle–invasive tumor of stage T2– T3a. Non–muscle invasive T1 tumor was present in four patients. Quality of life was assessed by continence, which was good in 10/13 patients. Three women needed CIC. Sexual function was tested by female sexual function index >20–30 and was scored at 84.61%. Conclusions The study provides evidence of safety and efficacy of radical cystectomy with sparing of genital organs in women aged 20 to 54 with urothelial carcinoma of the bladder. Oncological outcome for 5–15 years was good; continence and sexual function were good. This procedure should be considered when surgical approach appears to be feasible. The limitation of our findings is the small sample size of this case series. PMID:26251729

  10. Reversal of hypersplenism following orthotopic liver transplantation.

    PubMed Central

    Yanaga, K; Tzakis, A G; Shimada, M; Campbell, W E; Marsh, J W; Stieber, A C; Makowka, L; Todo, S; Gordon, R D; Iwatsuki, S

    1989-01-01

    The purpose of this study was to clarify the effect of orthotopic liver transplantation on hypersplenism. In a 1-year period from July 1, 1986 to June 30, 1987, 196 adult patients underwent 233 orthotopic liver transplantations. Of the 58 patients with hypersplenism who were analyzed in this study, hypersplenism was more commonly associated with postnecrotic cirrhosis than other kinds of liver disease (55.3% (47/85) vs. 14.5% (11/76); p less than 0.001). Postoperative platelet counts were statistically higher than preoperative values (p less than 0.05). The latest platelet counts were more than 100,000/mm3 in 53 patients (91.4%). Of the eight patients whose preoperative and postoperative spleen volumes could be compared, all showed the reduction in the spleen size (p less than 0.02). We conclude that orthotopic liver transplantation, which is a radical surgical procedure for portal hypertension, reverses hypersplenism. PMID:2667473

  11. Fluorescent Orthotopic Mouse Model of Pancreatic Cancer.

    PubMed

    Moreno, Jonathan A; Sanchez, Antonio; Hoffman, Robert M; Nur, Saima; Lambros, Maria P

    2016-01-01

    Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serum-free media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors. PMID:27685334

  12. Complications of Radical Cystectomy and Orthotopic Reconstruction

    PubMed Central

    Tan, Wei Shen; Lamb, Benjamin W.; Kelly, John D.

    2015-01-01

    Radical cystectomy and orthotopic reconstruction significant morbidity and mortality despite advances in minimal invasive and robotic technology. In this review, we will discuss early and late complications, as well as describe efforts to minimize morbidity and mortality, with a focus on ileal orthotopic bladder substitute (OBS). We summarise efforts to minimize morbidity and mortality including enhanced recovery as well as early and late complications seen after radical cystectomy and OBS. Centralisation of complex cancer services in the UK has led to a fall in mortality and high volume institutions have a significantly lower rate of 30-day mortality compared to low volume institutions. Enhanced recovery pathways have resulted in shorter length of hospital stay and potentially a reduction in morbidity. Early complications of radical cystectomy occur as a direct result of the surgery itself while late complications, which can occur even after 10 years after surgery, are due to urinary diversion. OBS represents the ideal urinary diversion for patients without contraindications. However, all patients with OBS should have regular long term follow-up for oncological surveillance and to identify complications should they arise. PMID:26697063

  13. Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney

    PubMed Central

    Song, Jeremy J; Guyette, Jacques; Gilpin, Sarah; Gonzalez, Gabriel; Vacanti, Joseph P; Ott, Harald C

    2013-01-01

    Over 100,000 individuals in the United States currently await kidney transplantation, while 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney’s architecture and function, and permit perfusion, filtration, secretion, absorption, and drainage of urine. We decellularized rat, porcine, and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells, then perfused these cell-seeded constructs in a whole organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused via their intrinsic vascular bed. When transplanted in orthotopic position in rat, the grafts were perfused by the recipient’s circulation, and produced urine via the ureteral conduit in vivo. PMID:23584091

  14. [Orthotopic liver transplantation: surgery research center's experience].

    PubMed

    Got'e, S V; Eramishantsev, A K; Tsirul'nikova, O M; Skipenko, O G; Filin, A V; Lokshin, L S; Kozhevnikov, V A; Eremenko, A A; Zhidkov, I L

    1997-01-01

    From 1990 to 1996, 178 patients with severe diffuse and advanced focal liver diseases with grave prognosis were observed for indications to orthotopic liver transplantation (OLT). According to the revealed indications and contraindications, 95 patients were enrolled for the procedure. Eighteen patients underwent 19 OLTs, including 1 urgent retransplantation and 3 living related graftings. Surgical techniques were conventional; with these, intraoperative mortality and biliary complications could be avoided. Long-term survival (6 to 68 months) was achieved in 8 recipients, including in those after liver retransplantation. Double or triple suppressive regimens were used. These included corticosteroids, cyclosporin A, azathioprine, antithymocytic globulin. The life quality of recipients promoted restoration of their working capacities. Two recipients gave birth to healthy babies.

  15. 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. PMID:23430518

  16. Replace Double Replacement

    NASA Astrophysics Data System (ADS)

    Martin, R. Bruce

    1999-01-01

    Reactions described as double replacements in high school texts are poorly described by this designation. The driving force for such reactions is precipitation of a solid derived from ions in solution or the production of water in acid-base reactions.

  17. Societal reintegration following cadaveric orthotopic liver transplantation

    PubMed Central

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

    2016-01-01

    Background Studies on patients’ societal reintegration following orthotopic liver transplantation (OLT) are scarce. Methods 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. Results 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. Conclusions 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. PMID:27275465

  18. Orthotopic and heterotopic ovarian tissue transplantation

    PubMed Central

    Demeestere, I.; Simon, P.; Emiliani, S.; Delbaere, A.; Englert, Y.

    2009-01-01

    BACKGROUND Transplantation of ovarian tissue is, at present, the only clinical option available to restore fertility using cryopreserved ovarian tissue. More than 30 transplantations of cryopreserved tissue have been reported, and six babies have been born, worldwide, following this procedure. Despite these encouraging results, it is essential to optimize the procedure by improving the follicular survival, confirming safety and developing alternatives. Here, we review the different factors affecting follicular survival and growth after grafting. METHODS Relevant studies were identified by searching Pubmed up to January 2009 with English language limitation. The following key words were used: (ovarian tissue or whole ovary) AND (transplantation) AND (cryopreservation or pregnancy). Using the literature and personal experience, we examined relevant data on the different exogenous and clinical factors affecting follicular development after grafting. RESULTS Clinical factors such as the patient's age and the transplantation sites influenced the lifespan of the graft. A heterotopic transplantation site is not optimal but offers some advantages and it may also promote the hormonal environment after a combined heterotopic and orthotopic transplantation. Exogenous factors such as antioxidants, growth factors or hormones were tested to improve follicular survival; however, their efficiency regarding further follicular development and fertility potential remains to be established. CONCLUSION Additional evidence is required to define optimal conditions for ovarian tissue transplantation. Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future. PMID:19474206

  19. 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

  20. Aspergillus Mediastinitis after Orthotopic Heart Transplantation: A Case Report.

    PubMed

    El-Sayed Ahmed, Magdy M; Almanfi, Abdelkader; Aftab, Muhammad; Singh, Steve K; Mallidi, Hari R; Frazier, O H

    2015-10-01

    A 55-year-old woman was admitted for orthotopic heart transplantation. Her medical history was notable for multiple cardiovascular problems, including ischemic cardiomyopathy that necessitated circulatory support with a left ventricular assist device. Five weeks after undergoing orthotopic heart transplantation, she developed Aspergillus calidoustus mediastinitis, for which she underwent a prolonged course of antifungal treatment that comprised (in sequence) posaconazole for 11 days, voriconazole for 10 days, and amphotericin B for 42 days. During this period, she also underwent repeated mediastinal drainage and sternal débridement, followed by sternal wiring and coverage with bilateral pectoralis advancement flaps. Four months postoperatively, she was discharged from the hospital with a successfully controlled infection and a healed sternum. To our knowledge, only 3 previous cases of Aspergillus mediastinitis after orthotopic heart transplantation have been reported in the literature, none of which was Aspergillus calidoustus.

  1. [Disorders of hemostasis in orthotopic liver transplantation in an experiment].

    PubMed

    Dement'eva, I I; Andrianova, M Iu; Paliulina, M V; Broun, N K; Zhidkov, I L; Gom'e, S V

    1995-01-01

    The study was undertaken to examine blood coagulative parameters in experimental orthotopic liver grafting. Plasma hemostatic parameters were studied in animals undergone successful and unsuccessful surgery. The preservation of a graft, anesthetization, and blood-substitute therapy were found to substantially affect the severity of hemostatic disorders. The liver-free period was characterized by changes in the fibrinolytic system and the activity of a plasma coagulation, by enhanced hypocoagulation, and thrombocytopenia. The findings suggest that timely correction of blood coagulative disorders is highly essential in orthotopic liver grafting. Prevention and prompt correction of hypocoagulation and thrombocytopenia are the most urgent.

  2. Caroli's disease and orthotopic liver transplantation.

    PubMed

    Habib, Shahid; Shakil, Obaid; Couto, Osvaldo F; Demetris, Anthony J; Fung, John J; Marcos, Amadeo; Chopra, Kapil

    2006-03-01

    Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver

  3. 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

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

    PubMed

    Sjöqvist, Sebastian; Jungebluth, Philipp; Lim, Mei Ling; Haag, Johannes C; Gustafsson, Ylva; Lemon, Greg; Baiguera, Silvia; Burguillos, Miguel Angel; 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

    2014-04-15

    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.

  5. Auxiliary partial orthotopic liver transplantation for Crigler-Najjar syndrome type I.

    PubMed Central

    Rela, M; Muiesan, P; Vilca-Melendez, H; Dhawan, A; Baker, A; Mieli-Vergani, G; Heaton, N D

    1999-01-01

    OBJECTIVE: To determine if auxiliary partial orthotopic liver transplantation (APOLT) has the long-term potential to correct the underlying abnormality in Crigler-Najjar syndrome type 1 (CNS1) without the need for total liver replacement. BACKGROUND: Orthotopic liver transplantation has been used successfully to replace the defective enzyme in CNS1. Experimental studies have shown that only 1% to 2% of the normal hepatocyte mass is needed for bilirubin conjugation. If APOLT corrects the underlying metabolic abnormality, it has the advantage of preserving the native liver, which would serve as a "safety net" should the graft fail, and there is the potential for gene therapy in the future with possible withdrawal of immunosuppression. METHODS: Seven APOLT procedures were performed in six recipients with CNS1. Median age at transplantation was 10.5 years. Six transplants were performed as a left auxiliary liver transplant, and one was performed as a right auxiliary liver transplant. Median serum bilirubin level at transplantation was 320 micromol/L. All patients required 12 to 16 hours of phototherapy daily before the transplant to maintain serum bilirubin levels between 250 and 350 micromol/L. RESULTS: Median serum bilirubin level was 50 micromol/L at day 5 after the transplant and 23 micromol/L at a median follow-up of 32 months. In four children, early severe acute rejection developed, requiring conversion to tacrolimus; one underwent a second transplant for chronic rejection and graft atrophy but died from lymphoproliferative disease 6 months after the second transplant. CONCLUSIONS: This report shows that APOLT is technically feasible and provides adequate hepatocyte mass to correct the underlying metabolic abnormality in CNS1. PMID:10203091

  6. Hip Replacement

    MedlinePlus

    ... replacement is an operation in which a damaged hip joint is removed and replaced with an artificial joint. ... are many medical conditions that can damage the hip joint. (Watch the video to learn about what goes ...

  7. Hip Replacement

    MedlinePlus

    ... surgeon removes damaged cartilage and bone from your hip joint and replaces them with new, man-made parts. A hip replacement can Relieve pain Help your hip joint work better Improve walking and other movements The ...

  8. Ankle replacement

    MedlinePlus

    Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... You may not be able to have a total ankle replacement if you have had ankle joint infections ...

  9. Knee Replacement

    MedlinePlus

    Knee replacement is surgery for people with severe knee damage. Knee replacement can relieve pain and allow you to ... Your doctor may recommend it if you have knee pain and medicine and other treatments are not ...

  10. Orthotopic models of pediatric brain tumors in zebrafish.

    PubMed

    Eden, C J; Ju, B; Murugesan, M; Phoenix, T N; Nimmervoll, B; Tong, Y; Ellison, D W; Finkelstein, D; Wright, K; Boulos, N; Dapper, J; Thiruvenkatam, R; Lessman, C A; Taylor, M R; Gilbertson, R J

    2015-03-26

    High-throughput screens (HTS) of compound toxicity against cancer cells can identify thousands of potential new drug-leads. But only limited numbers of these compounds can progress to expensive and labor-intensive efficacy studies in mice, creating a 'bottle neck' in the drug development pipeline. Approaches that triage drug-leads for further study are greatly needed. Here we provide an intermediary platform between HTS and mice by adapting mouse models of pediatric brain tumors to grow as orthotopic xenografts in the brains of zebrafish. Freshly isolated mouse ependymoma, glioma and choroid plexus carcinoma cells expressing red fluorescence protein were conditioned to grow at 34 °C. Conditioned tumor cells were then transplanted orthotopically into the brains of zebrafish acclimatized to ambient temperatures of 34 °C. Live in vivo fluorescence imaging identified robust, quantifiable and reproducible brain tumor growth as well as spinal metastasis in zebrafish. All tumor xenografts in zebrafish retained the histological characteristics of the corresponding parent mouse tumor and efficiently recruited fish endothelial cells to form a tumor vasculature. Finally, by treating zebrafish harboring ERBB2-driven gliomas with an appropriate cytotoxic chemotherapy (5-fluorouracil) or tyrosine kinase inhibitor (erlotinib), we show that these models can effectively assess drug efficacy. Our data demonstrate, for the first time, that mouse brain tumors can grow orthotopically in fish and serve as a platform to study drug efficacy. As large cohorts of brain tumor-bearing zebrafish can be generated rapidly and inexpensively, these models may serve as a powerful tool to triage drug-leads from HTS for formal efficacy testing in mice. PMID:24747973

  11. Orthotopic non-metastatic and metastatic oral cancer mouse models.

    PubMed

    Bais, Manish V; Kukuruzinska, Maria; Trackman, Philip C

    2015-05-01

    Oral cancer is characterized by high morbidity and mortality with a predisposition to metastasize to different tissues, including lung, liver, and bone. Despite progress in the understanding of mutational profiles and deregulated pathways in oral cancer, patient survival has not significantly improved over the past decades. Therefore, there is a need to establish in vivo models that recapitulate human oral cancer metastasis to evaluate therapeutic potential of novel drugs. Here we report orthotopic tongue cancer nude mouse models to study oral cancer growth and metastasis using human metastatic (UMSCC2) and non-metastatic (CAL27) cell lines, respectively. Transduction of these cell lines with lentivirus expressing red fluorescent protein (DsRed) followed by injection into tongues of immunodeficient mice generated orthotopic tongue tumors that could be monitored for growth and metastasis by fluorescence measurement with an in vivo Imaging System (IVIS 200). The growth rates of CAL27-DsRed induced tumors were higher than UMSCC2-DsRed tumors after day 15, while UMSCC2-DsRed tumors revealed metastasis beginning on day 21. Importantly, UMSCC2 tumors metastasized to a number of tissues including the submandibular gland, lung, kidney, liver, and bone. Further, immunohistochemical analyses of tongue tumors induced by CAL27 and UMSCC2 cells revealed elevated expression of components of protumorigenic pathways deregulated in human cancers, including Cyclin D1, PCNA, Ki-67, LSD1, LOXL2, MT-MMP1, DPAGT1, E-cadherin, OCT4A, and H3K4me1/2. These orthotopic mouse models are likely to be useful tools for gaining insights into the activity and mechanisms of novel oral cancer drug candidates.

  12. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland.

    PubMed

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable.

  13. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland.

    PubMed

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

  14. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland

    PubMed Central

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

  15. Patient-derived orthotopic xenografts: better mimic of metastasis than subcutaneous xenografts.

    PubMed

    Hoffman, Robert M

    2015-08-01

    The majority of human solid tumours do not metastasize when grown subcutaneously in immunocompromised mice; this includes patient-derived xenograft (PDX) models. However, orthotopic implantation of intact tumour tissue can lead to metastasis that mimics that seen in patients. These patient-derived orthotopic xenograft (PDOX) models have a long history and might better recapitulate human tumours than PDX models.

  16. Treatment Experience of Severe Abdominal Infection after Orthotopic Liver Transplantation

    PubMed Central

    Wang, Y-G; Wu, J-S; Jiang, B; Wang, J-H; Liu, C-P; Peng, C; Tian, B-Z

    2015-01-01

    ABSTRACT This study aims to investigate the causes and treatment experience of severe abdominal infection after orthotopic liver transplantation. Clinical data were retrospectively analysed in perioperative severe abdominal infection of 186 orthotopic liver transplantation cases from March 2004 to November 2011. Among the 186 patients, 16 cases had severe abdominal infection: five cases had bile duct anastomotic leakage-inducing massive hydrops and infection under liver interstice, 10 cases had extensive bleeding of surgical wound leading to massive haematocele and infection around the liver, and one case had postoperative lower oesophageal fistula leakage causing massive hydrops and infection under the left diaphragm. After definite diagnosis, 12 cases underwent surgery within three days, with no death. Among the four cases that underwent surgery three days after diagnosis, one case died of multiple-organ failure five days after abdominal cavity exploration, which was performed 21 days after liver transplantation. Severe abdominal infections after liver transplantation were the most common causes of death in perioperative liver transplantation. Comprehensive treatment with efficacious antibiotics, multiple-organ support, controlled surgical removal of the lesion, and adequate drainage establishment was the key to the entire treatment. PMID:26426173

  17. Orthotopic liver transplantation for giant liver haemangioma: A case report.

    PubMed

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-12-24

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  18. Development and characterization of a human orthotopic neuroblastoma xenograft

    PubMed Central

    Stewart, Elizabeth; Shelat, Anang; Bradley, Cori; Chen, Xiang; Federico, Sara; Thiagarajan, Suresh; Shirinifard, Abbas; Bahrami, Armita; Pappo, Alberto; Qu, Chunxu; Finkelstein, David; Sablauer, Andras; Dyer, Michael A.

    2016-01-01

    Neuroblastoma is a pediatric cancer of the developing sympathoadrenal lineage. The tumors are known to develop from the adrenal gland or paraspinal ganglia and have molecular and cellular features of sympathetic neurons such as dense core vesicles and catecholamine production. Here we present the detailed molecular, cellular, genetic and epigenetic characterization of an orthotopic xenograft derived from a high-risk stage 4 neuroblastoma patient. Overall, the xenografted tumor retained the high risk features of the primary tumor and showed aggressive growth and metastasis in the mouse. Also, the genome was preserved with no additional copy number variations, structural variations or aneuploidy. There were 13 missense mutations identified in the xenograft that were not present in the patient’s primary tumor and there were no new nonsense mutations. None of the missense mutations acquired in the xenograft were in known cancer genes. We also demonstrate the feasibility of using the orthotopic neuroblastoma xenograft to test standard of care chemotherapy and molecular targeted therapeutics. Finally, we optimized a new approach to produce primary cultures of the neuroblastoma xenografts for high-throughput drug screening which can be used to test new combinations of therapeutic agents for neuroblastoma. PMID:25863122

  19. 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

  20. Tissue Engineered Scaffolds for an Effective Healing and Regeneration: Reviewing Orthotopic Studies

    PubMed Central

    2014-01-01

    It is commonly stated that tissue engineering is the most promising approach to treat or replace failing tissues/organs. For this aim, a specific strategy should be planned including proper selection of biomaterials, fabrication techniques, cell lines, and signaling cues. A great effort has been pursued to develop suitable scaffolds for the restoration of a variety of tissues and a huge number of protocols ranging from in vitro to in vivo studies, the latter further differentiating into several procedures depending on the type of implantation (i.e., subcutaneous or orthotopic) and the model adopted (i.e., animal or human), have been developed. All together, the published reports demonstrate that the proposed tissue engineering approaches spread toward multiple directions. The critical review of this scenario might suggest, at the same time, that a limited number of studies gave a real improvement to the field, especially referring to in vivo investigations. In this regard, the present paper aims to review the results of in vivo tissue engineering experimentations, focusing on the role of the scaffold and its specificity with respect to the tissue to be regenerated, in order to verify whether an extracellular matrix-like device, as usually stated, could promote an expected positive outcome. PMID:25250319

  1. Anesthesia in orthotopic liver transplantation. Report of 8 cases.

    PubMed

    Shiao, J; Haosheng, B; Zicheng, M; Chongrong, G

    1981-09-01

    The anesthetic management of orthotopic liver transplantation has become a new problem with special requirements. From the anesthetist's point of view the operation is divided into four phases: the first is the phase of removal of the diseased liver, characterized by heavy bleeding; the second is the anhepatic phase, dominated by a sudden reduction of blood return to the heart due to cross-clamping of inferior vena cava; the third is the phase of partial re-establishment of circulation of the donated liver, marked by a progressive drop in body temperature and great changes in acid-base equilibrium and electrolytes, especially potassium, and disturbances of blood coagulation potassium, and disturbances of blood coagulation; the fourth is the phase of release of the clamps from the inferior vena cava, which causes a rise in the central venous and systolic pressures, and may also aggravate the metabolic acidosis. Eight cases of orthotopic liver transplantation for late-stage unresectable hepatocarcinoma have been operated upon under combined neurolept anesthesia in recent 3 years. The age of the patients is between 29-50 years. We think that neurolept analgesia with the combined use of gamma-OH, diazepam, ketamine and gallamine is one of the safest methods of anesthesia, which has a minimal toxicity to the liver, a smooth induction and rapid recovery of consciousness, and puts little burden on the circulation. The postoperative survival of first seven patients was between 6-264 days. There were no postanesthetic complications in our series. The authors conclude that the proper choice of anesthesia, careful monitoring and judicious management of the patients during the various phases of operation, the maintenance of good condition of the donated liver and skillful surgical technique are the basic requirements for successful transplantation. PMID:7025697

  2. [Estrogen replacement].

    PubMed

    Søgaard, A J; Berntsen, G K; Magnus, J H; Tollan, A

    1998-02-10

    Recent research on long-term postmenopausal hormone replacement therapy (HRT) indicates a positive effect on both total mortality and morbidity. This has raised the question of widespread preventive long-term use of HRT. Possible side-effects and ideological issues related to preventive HRT have led to debate and uncertainty among health professionals, in the media, and in the population at large. In order to evaluate the level of knowledge about and attitudes towards HRT, a randomly selected group of 737 Norwegian women aged 16-79 was interviewed by the Central Bureau of Statistics. One in three women had received information about HRT in the last two years, mainly through weekly magazines and physicians. The proportion who answered the questions on knowledge correctly varied from 36% to 47%. Those who had been given information by a physician possessed accurate knowledge, had more positive attitudes towards HRT and were more willing to use HRT than women who had reviewed information through other channels. Women with a higher level of education were better informed and more knowledgeable than others, but were nevertheless more reluctant to use HRT than those who were less educated. The limited number of women who actually receive information on HRT, the low level of knowledge and the ambivalent attitudes toward HRT are a major challenge to the public health service.

  3. Nicotine replacement therapy

    MedlinePlus

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012 Nov 14;11: ...

  4. 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.

  5. A New Rat Model for Orthotopic Abdominal Wall Allotransplantation

    PubMed Central

    Lao, William W.; Wang, Yen-Ling; Ramirez, Alejandro E.; Cheng, Hui-Yun

    2014-01-01

    Background: Abdominal wall, one of the most commonly transplanted composite tissues, is less researched and lacking animal models. Its clinical necessities were emphasized in multiple case series to reconstruct large abdominal defects. Previous animal models have only studied components of the abdominal wall transplant. We describe findings from a new model that more likely reflect clinical transplantation. Methods: Full-thickness hemiabdominal wall flap was procured from Brown Norway (BN) rats and transplanted to an orthotopic defect on Lewis rats. Three groups were studied: group 1: Lewis to Lewis syngeneic; group 2: BN to Lewis control; and group 3: BN to Lewis with postoperative cyclosporine. Vascular imaging and cross vessel section were performed along with full-thickness abdominal wall. Immune cell profiling with flow cytometry at different time points was studied in all groups. Results: Syngeneic group had no rejection. Control group consistently showed rejection around postoperative day 6. With cyclosporine treatment, however, transplant and recipient tissue integration was observed. Flow cytometry revealed that innate immunity is responsible for the initial inflammatory events following abdominal wall engraftment. Adaptive immunity cells, specifically interferon-γ-producing T helper (Th) 1 and interleukin-17-producing Th17 cells, dramatically and positively correlate with rejection progression of abdominal wall transplants. Conclusions: Technical, histological, and immunological aspects of a new rat model are described. These results give clues to what occurs in human abdominal wall transplantation. In addition, Th1, a proinflammatory cell, was found to be a potential biomarker for allograft rejection. PMID:25289329

  6. An Orthotopic Murine Model of Human Prostate Cancer Metastasis

    PubMed Central

    Pavese, Janet; Ogden, Irene M.; Bergan, Raymond C.

    2013-01-01

    Our laboratory has developed a novel orthotopic implantation model of human prostate cancer (PCa). As PCa death is not due to the primary tumor, but rather the formation of distinct metastasis, the ability to effectively model this progression pre-clinically is of high value. In this model, cells are directly implanted into the ventral lobe of the prostate in Balb/c athymic mice, and allowed to progress for 4-6 weeks. At experiment termination, several distinct endpoints can be measured, such as size and molecular characterization of the primary tumor, the presence and quantification of circulating tumor cells in the blood and bone marrow, and formation of metastasis to the lung. In addition to a variety of endpoints, this model provides a picture of a cells ability to invade and escape the primary organ, enter and survive in the circulatory system, and implant and grow in a secondary site. This model has been used effectively to measure metastatic response to both changes in protein expression as well as to response to small molecule therapeutics, in a short turnaround time. PMID:24084571

  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. An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis.

    PubMed

    Paschall, Amy V; Liu, Kebin

    2016-01-01

    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. PMID:27584043

  9. Orthotopic liver transplantation in liver-based metabolic disorders.

    PubMed

    Mowat, A P

    1992-01-01

    The efficacy of orthotopic liver transplantation (OLT) in the management of more common liver-based metabolic disorders associated with severe liver damage, alpha-1-antitrypsin deficiency (PIZZ), Wilson disease and tyrosinaemia has been demonstrated and indications defined. An early mortality in excess of 15% and finite resources limit its use. Phenotypic heterogeneity make the precise indication in other disorders less certain. In disorders in which endstage liver disease is less frequent such as cystic fibrosis, haemochromatosis and galacosaemia it has been a very effective therapy. It has been used with encouraging results in disorders in which the liver is structurally normal such as Crigler-Najjar type I, primary hyperoxaluria type I and primary hypercholesterolaemia. In these it should be performed before there is permanent damage to brain, kidneys or heart. OLT in the short term prevents hyperammonaemic coma in urea cycle defects and may prevent extrahepatic disease in glycogen storage disease type IV. Its limitation in reversing all metabolic effects in these and other disorders is discussed. It is ineffective in protoporphyria or Niemann Pick disease type II (Sea Blue Histiocyte syndrome) in which the transplanted liver acquires the lesions of the initial disorder and extrahepatic features progress. Early referral provides optimum circumstances to assess the benefits of OLT as compared with those of other forms of management and to achieve transplantation at the ideal time. The place of OLT in management will require constant review as metabolic disorders are better defined, new forms of therapy evolve and as techniques of liver transplantation and modes of immunosuppression improve.

  10. SPLIT TOLERANCE INDUCED BY ORTHOTOPIC LIVER TRANSPLANTATION IN MICE1

    PubMed Central

    Dahmen, Uta; Qian, Shiguang; Rao, Abdul S.; Demetris, Anthony J.; Fu, Fumin; Sun, Hong; Gao, Lan; Fung, John J.; Starzl, Thomas E.

    2011-01-01

    Spontaneous orthotopic liver allograft acceptance associated with microchimerism in mice induces tolerance to subsequent skin or heart transplants from the donor but not third-party animals. Despite in vivo hyporesponsiveness, in vitro MLC and CTL assays showed continuing antidonor reactivity. Cells isolated from recipients’ spleens and grafted livers, when tested in MLC and CTL assays, were antidonor reactive out to 3 months to the same degree as splenocytes obtained from either naive or presensitized (with skin or heart) mice. Nevertheless, passive transfer of splenocytes or liver lymphocytes from liver tolerant mice, but not naive or sensitized donor strain mice, were able to prolong skin graft survival significantly in naive irradiated recipients. By using a strain combination in which the donor but not the recipient expressed the stimulatory endogenous super-Ag (Mlsf), it was possible to determine whether super-Ag-reactive T cells bearing Vβ5 and Vβ11 were deleted or anergic. Phenotypic analysis of cells isolated from recipients’ spleens and grafted livers (up to 90 days after transplant), when compared with naive animals, showed no significant difference in Vβ5 and Vβ11 TCR expression. Additionally, when these isolated spleen cells were tested for antibody-mediated stimulation, both anti-Vβ5 and Vβ11 TCR mAb led to marked proliferation of cells obtained from naive and liver-transplanted recipients, but as expected, proliferation was very low in cells from naive donors. These results suggest that liver transplantation induces donor-specific tolerance in vivo, which may not be reflected in in vitro proliferative and cytotoxicity assays (split tolerance). Furthermore, this tolerance does not seem to be induced by clonal deletion or anergy of minor-lymphocyte-stimulating-antigen-reactive T cells in the recipients. PMID:8036695

  11. Current status of auxiliary partial orthotopic liver transplantation for acute liver failure.

    PubMed

    Rela, Mohamed; Kaliamoorthy, Ilankumaran; Reddy, Mettu Srinivas

    2016-09-01

    Auxiliary partial orthotopic liver transplantation (APOLT) is a technique of liver transplantation (LT) where a partial liver graft is implanted in an orthotopic position after leaving behind a part of the native liver. APOLT was previously considered technically challenging with results inferior to orthotopic liver transplantation. Results of this procedure have continued to improve with improving surgical techniques and a better understanding of the natural history of acute liver failure (ALF) and liver regeneration. The procedure is being increasingly accepted as a valid treatment option for ALF-especially in children. This article reviews the historical background to this operation, advances in the technique, and its current place in the management of ALF. Liver Transplantation 22 1265-1274 2016 AASLD. PMID:27357489

  12. 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

  13. Orthotopic Heart Transplantation in an Adult Patient with Heterotaxy Syndrome: Surgical Implications.

    PubMed

    González-López, María-Teresa; Pérez-Caballero-Martínez, Ramón; Amoros-Rivera, Carlos; Zamorano-Serrano, José; Pita-Fernández, Ana-María; Gil-Jaurena, Juan-Miguel

    2015-12-01

    Modified techniques for orthotopic heart transplantation are mandatory when complex congenital anomalies are associated in adult patients. An unusual case of a heterotaxy syndrome and dilated cardiomyopathy following mitral ring annuloplasty is presented in a 62-year-old male. Orthotopic cardiac transplantation was performed by using a modified operative strategy: selective peripheral and central venous cannulation according to the thoraco-abdominal venous challenges, biatrial technique, and preservation of venous drainage via the native coronary sinus. We discuss the anatomical features of heterotaxy in adult patients and surgical approaches when heart transplantation is needed. PMID:26450654

  14. Orthotopic Heart Transplantation in Patients with Univentricular Physiology

    PubMed Central

    Michielon, Guido; Carotti, Adriano; Pongiglione, Giacomo; Cogo, Paola; Parisi, Francesco

    2011-01-01

    Parallel advancements in surgical technique, preoperative and postoperative care, as well as a better understanding of physiology in patients with duct-dependent pulmonary or systemic circulation and a functional single ventricle, have led to superb results in staged palliation of most complex congenital heart disease (CHD) [1]. The Fontan procedure and its technical modifications have resulted in markedly improved outcomes of patients with single ventricle anatomy [2,3,4]. The improved early survival has led to an exponential increase of the proportion of Fontan patients surviving long into adolescence and young adulthood [5]. Improved early and late survival has not yet abolished late mortality secondary to myocardial failure, therefore increasing the referrals for cardiac transplantation [6]. Interstage attrition [7] is moreover expected in staged palliation towards completion of a Fontan-type circulation, while Fontan failure represents a growing indication for heart transplantation [8]. Heart transplantation has therefore become the potential “fourth stage” [9] or a possible alternative to a high-risk Fontan operation [10] in a strategy of staged palliation for single ventricle physiology. Heart transplant barely accounts for 16% of pediatric solid organ transplants [11]. The thirteenth official pediatric heart transplantation report- 2010 [11] indicates that pediatric recipients received only 12.5% of the total reported heart transplants worldwide. Congenital heart disease is not only the most common recipient diagnosis, but also the most powerful predictor of 1-year mortality after OHT. Results of orthotopic heart transplantations (OHT) for failing single ventricle physiology are mixed. Some authors advocate excellent early and mid-term survival after OHT for failing Fontan [9], while others suggest that rescue-OHT after failing Fontan seems unwarranted [10]. Moreover, OHT outcome appears to be different according to the surgical staging towards the

  15. Hip joint replacement

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002975.htm Hip joint replacement To use the sharing features on this page, please enable JavaScript. Hip joint replacement is surgery to replace all or part ...

  16. 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. PMID:20936468

  17. Temporal Characterization of Lymphatic Metastasis in an Orthotopic Mouse Model of Oral Cancer

    PubMed Central

    Szaniszlo, Peter; Fennewald, Susan M.; Qiu, Suimin; Kantara, Carla; Shilagard, Tuya; Vargas, Gracie; Resto, Vicente A.

    2013-01-01

    Background Overall mortality rate of head and neck squamous cell carcinoma (HNSCC) has not improved over the past 30 years; mostly due to high treatment failure rate among patients with regionally metastatic disease. To better understand the pathobiological processes leading to lymphatic metastasis development there is an urgent need for relevant animal models. Methods HNSCC cell lines were implanted into the tongues of athymic, nude mice. Histology, immunohistochemistry and ex vivo two-photon microscopy were used to evaluate tumor progress and spread. Results Orthotopic xenografts of different HNSCC cell lines produced distinct patterns of survival, tumor histology, disease progression rate, and lymph node metastasis development. Remarkably, all injected cell types reached the lymph nodes within 24 hours after injection, but not all developed metastasis. Conclusions This orthotopic xenograft model closely mimics several characteristics of human cancer and could be extremely valuable for translational studies focusing on lymphatic metastasis development and pathobiology. PMID:24115017

  18. SlimQuick™-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation

    PubMed Central

    Whitsett, Maureen; Rossi, Simona

    2014-01-01

    Green tea extract is a popular ingredient in herbal weight loss supplements. There have been reports of hepatotoxicity associated with the use of dietary supplements, some of these cases lead to fatal outcomes. To our knowledge, we report the first case of fulminant hepatic failure requiring orthotopic liver transplantation caused by SlimQuick™ (Wellnx Life Sciences, Wilmington, DE), a widely available weight loss supplement containing green tea extract. PMID:26157882

  19. Immunotherapy of HPV-associated cancer: DNA/plant-derived vaccines and new orthotopic mouse models.

    PubMed

    Venuti, Aldo; Curzio, Gianfranca; Mariani, Luciano; Paolini, Francesca

    2015-10-01

    Under the optimistic assumption of high-prophylactic HPV vaccine coverage, a significant reduction of cancer incidence can only be expected after decades. Thus, immune therapeutic strategies are needed for persistently infected individuals who do not benefit from the prophylactic vaccines. However, the therapeutic strategies inducing immunity to the E6 and/or E7 oncoprotein of HPV16 are more effective for curing HPV-expressing tumours in animal models than for treating human cancers. New strategies/technologies have been developed to improve these therapeutic vaccines. Our studies focussed on preparing therapeutic vaccines with low-cost technologies by DNA preparation fused to either plant-virus or plant-toxin genes, such as saporin, and by plant-produced antigens. In particular, plant-derived antigens possess an intrinsic adjuvant activity that makes these preparations especially attractive for future development. Additionally, discrepancy in vaccine effectiveness between animals and humans may be due to non-orthotopic localization of animal models. Orthotopic transplantation leads to tumours giving a more accurate representation of the parent tumour. Since HPV can cause cancer in two main localizations, anogenital and oropharynx area, we developed two orthotopic tumour mouse models in these two sites. Both models are bioluminescent in order to follow up the tumour growth by imaging and are induced by cell injection without the need to intervene surgically. These models were utilized for immunotherapies with genetic or plant-derived therapeutic vaccines. In particular, the head/neck orthotopic model appears to be very promising for studies combining chemo-radio-immune therapy that seems to be very effective in patients.

  20. Immunotherapy of HPV-associated cancer: DNA/plant-derived vaccines and new orthotopic mouse models.

    PubMed

    Venuti, Aldo; Curzio, Gianfranca; Mariani, Luciano; Paolini, Francesca

    2015-10-01

    Under the optimistic assumption of high-prophylactic HPV vaccine coverage, a significant reduction of cancer incidence can only be expected after decades. Thus, immune therapeutic strategies are needed for persistently infected individuals who do not benefit from the prophylactic vaccines. However, the therapeutic strategies inducing immunity to the E6 and/or E7 oncoprotein of HPV16 are more effective for curing HPV-expressing tumours in animal models than for treating human cancers. New strategies/technologies have been developed to improve these therapeutic vaccines. Our studies focussed on preparing therapeutic vaccines with low-cost technologies by DNA preparation fused to either plant-virus or plant-toxin genes, such as saporin, and by plant-produced antigens. In particular, plant-derived antigens possess an intrinsic adjuvant activity that makes these preparations especially attractive for future development. Additionally, discrepancy in vaccine effectiveness between animals and humans may be due to non-orthotopic localization of animal models. Orthotopic transplantation leads to tumours giving a more accurate representation of the parent tumour. Since HPV can cause cancer in two main localizations, anogenital and oropharynx area, we developed two orthotopic tumour mouse models in these two sites. Both models are bioluminescent in order to follow up the tumour growth by imaging and are induced by cell injection without the need to intervene surgically. These models were utilized for immunotherapies with genetic or plant-derived therapeutic vaccines. In particular, the head/neck orthotopic model appears to be very promising for studies combining chemo-radio-immune therapy that seems to be very effective in patients. PMID:26138695

  1. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice

    PubMed Central

    Wu, Tao; Heuillard, Emilie; Lindner, Véronique; Bou About, Ghina; Ignat, Mihaela; Dillenseger, Jean-Philippe; Anton, Nicolas; Dalimier, Eugénie; Gossé, Francine; Fouré, Gael; Blindauer, Franck; Giraudeau, Céline; El-Saghire, Hussein; Bouhadjar, Mourad; Calligaro, Cynthia; Sorg, Tania; Choquet, Philippe; Vandamme, Thierry; Ferrand, Christophe; Marescaux, Jacques; Baumert, Thomas F.; Diana, Michele; Pessaux, Patrick; Robinet, Eric

    2016-01-01

    The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging. PMID:27739457

  2. 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

  3. Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique.

    PubMed

    Ni, Jie; Cozzi, Paul; Hung, Tzong-Tyng; Hao, Jingli; Graham, Peter; Li, Yong

    2016-02-01

    Prostate cancer (CaP) is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D) ultrasound system equipped with photoacoustic (PA) imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8). Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r(2) = 0.948, 0.955, and 0.953, respectively) and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001). The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research.

  4. [Anatomic orthotopic heart transplantation: the surgical characteristics and the advantages of the method].

    PubMed

    Dzemeshkevich, S L; Ivanov, A S; Rykunov, I E; Kuznetsova, L M; Trekova, N A; Poplavskiĭ, I V; Belous, A E; Zhidkov, I L; Koseros, Kh; Eremenko, A A; Chaus, N I

    1998-01-01

    Standard technique of establishment of interatrial anastomoses allows to carry out orthotopic transplantation of the heart quickly and reliably. However the accumulation of collective experience evidences about a number of unavoidable shortcomings of such operation: rhythm disturbances, worsening of hemodynamics in discordant atrial contractions of recipient and donor, atrio-ventricular valve insufficiency, thromboembolism, coronary fistulas. Since 1990 in RRCS 25 operations were carried out with the use of standard technique and we also met with the risk of developing the above complications. In experiment on 30 mongrel dogs the technique of anatomical, truly orthotopic transplantation of the heart with six anastomoses was developed: left pulmonary veins with a common cuff, separate anastomoses of the superior and inferior caval veins, anastomoses of aorta and pulmonary artery. Particular attention was paid to developing of original surgical modes for prophylaxis of stenoses in the area of anastomoses of pulmonary and caval veins. In 1997 the anatomical technique of heart transplantation was successfully introduced by us into clinical practice. Clinical electrophysiological, echocardiographic and functional examinations have confirmed the results of the experiments and have evidenced for substantial advantages of the anatomical technique of orthotopic transplantation of the heart. By reliability the new operation is not inferior to standard method of N. Shumway.

  5. Is Duct to Duct biliary Anastomosis the Rule in Orthotopic Liver Transplantation?

    PubMed

    Selvakumar, N; Saha, Brig Anupam; Naidu, Surg Capt Sudeep

    2013-10-01

    Biliary complications after Liver Transplantation continue to be the major cause of morbidity in 11-25 % of patients. Biliary complications in patients who underwent orthotopic liver transplantation (OLT) at our institute between March 2007 and June 2010 were analyzed retrospectively. 32 patients underwent Deceased Donor Liver Transplantation (DDLT) and in 12 patients Living Donor Liver Transplantation (LDLT) was done. No patients were lost to follow up. Follow up ranged between 4 and 44 months. During the study period, 44 patients underwent orthotopic liver transplantation. Patients were divided into two groups: Biliary Complications group (BC) n = 5 and Non Biliary Complications group (NBC) n = 39. Biliary complications occurred in 15.9 % of patients. Bile leaks accounted for majority of biliary complications. Fifteen variables were analyzed as possible risk factors for biliary complications. Of these, split grafts, duct to duct biliary anastomosis and total blood loss were statistically significant (P < 0.05) for biliary complications. Endoscopic treatment was successful in managing biliary complications in 75 % of patients. Biliary complications are the most common major complications in orthotopic liver transplantation. Significant risk factors are split liver grafts and duct to duct biliary anastomosis. Increased blood loss is a predictor for post operative biliary complications. These complications should be managed by endoscopic interventions. Surgery is indicated following failure of endoscopic interventions. PMID:24426478

  6. Hepatic Dysfunction and Survival After Orthotopic Heart Transplantation: Application of the MELD Scoring System for Outcome Prediction

    PubMed Central

    Chokshi, Aalap; Cheema, Faisal H.; Schaefle, Kenneth J.; Jiang, Jeffrey; Collado, Elias; Shahzad, Khurram; Khawaja, Tuba; Farr, Maryjane; Takayama, Hiroo; Naka, Yoshifumi; Mancini, Donna; Schulze, P. Christian

    2012-01-01

    BACKGROUND The prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation. METHODS Data of 617 adult patients (75% males, mean age of 53±12 years, mean BMI of 25±4 and mean ejection fraction of 19±9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard model for end Stage liver disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anticoagulation. RESULTS Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25 and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathological values decreased significantly except ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up. CONCLUSIONS In this large, single-center retrospective study, we demonstrate dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome following OHT. Therefore, preoperative liver dysfunction has a significant impact on survival of patients after cardiac transplantation. PMID:22458996

  7. Ion replacement electrorefining

    SciTech Connect

    Willit, J.L.; Tomczuk, Z.; Miller, W.E.; Laidler, J.J.

    1994-04-01

    We are developing a two-step electrochemical process for purifying and separating metals called ion replacement electrorefining. In each step, metal cations formed by oxidation at an electrode replace other metal cations that are reduced at another elecmae. Using this approach, we have separated or purified uranium, dysprosium, and lanthanum on a laboratory scale. This paper explains the ion replacement concept and presents results of these demonstration experiments.

  8. Radiation Source Replacement Workshop

    SciTech Connect

    Griffin, Jeffrey W.; Moran, Traci L.; Bond, Leonard J.

    2010-12-01

    This report summarizes a Radiation Source Replacement Workshop in Houston Texas on October 27-28, 2010, which provided a forum for industry and researchers to exchange information and to discuss the issues relating to replacement of AmBe, and potentially other isotope sources used in well logging.

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

    PubMed Central

    Miller, Amy; Burson, Hannah; Söling, Ariane

    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

  10. Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models.

    PubMed

    Rao, Quan; You, Abin; Guo, Zhenglong; Zuo, Bingfeng; Gao, Xianjun; Zhang, Ti; Du, Zhi; Wu, Chenxuan; Yin, HaiFang

    2016-01-01

    Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters--the latency period, take rates, pathological features and metastatic rates--were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5 cm (longitudinal diameter) tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients. Our study

  11. Creation of a murine orthotopic hepatoma model with intra-abdominal metastasis

    PubMed Central

    Harris, Jamie; Kajdacsy-Balla, Andre; Chiu, Bill

    2016-01-01

    Aim: To create an orthotopic hepatoma model with local metastasis monitored with ultrasound could be created as a platform for testing new treatments. Background: Hepatoma accounts for 25% of liver tumors in children with poor overall survival. Intraabdominal metastasis are present in 35% of patients at time of diagnosis. We hypothesized that an orthotopic tumor model with local metastasis could be created as a platform for testing treatment modalities and could be monitored with ultrasound. Patients and methods: One million human hepatoma cells (Hep3B) were injected into the left lobe of the liver of immunocompromised mice. Tumor volume was monitored with high frequency-ultrasound until it reached 1,000mm3. At that time animals were sacrificed and examined for gross metastatic disease. Tumor sections were analyzed with hematoxylin and eosin (H&E) staining. Results: Tumor formed in 8/15 mice. The tumor was detected as small as 19.59mm3 on ultrasound. Of the forming tumors, tumor size was 145±177.93mm3 at 60 days post-injection, 665±650.39mm3 at 67 days, and reached >1000mm3 by 76.6±9.9 days. At necropsy, four mice (50%) had tumor only within the liver, four (50%) had additional tumors in omentum, pelvis and peritoneum. H&E showed tumor within the normal liver parenchyma, with multiple mitotic figures, small areas of necrosis, and hemorrhage within the tumor. Conclusion: We have successfully established an orthotopic hepatoma murine model, with a local metastatic rate of 50%. Non-invasive tumor monitoring is feasible via ultrasound. PMID:27458509

  12. Establishment of a dual-color fluorescence tracing orthotopic transplantation model of hepatocellular carcinoma

    PubMed Central

    CHEN, QIAN; WANG, XIAOPING; WU, HAO; WANG, HUI; ZHU, MINGAO; WANG, ROUSHU; WU, YING; ZHANG, LUYAO; MENG, QIAO; SONG, RANRAN; ZHUANG, ZHIXIANG; HUANG, QIANG

    2016-01-01

    Different experimental models of hepatocellular carcinoma (HCC) have been used to investigate the biological mechanisms of hepatocarcinogenesis and its progression. However, previous studies have highlighted the difficulty of distinguishing between the tumor cells and stroma in experimental models of HCC. Therefore the aim of the present study was to establish a red-green dual-color fluorescence tracing orthotopic transplantation model of HCC, and investigate its practical values. Stable high red fluorescent protein (RFP)-expressing HepG2 human hepatoma cells and Hepa1-6 mice hepatoma cells were injected into the right liver lobe of green fluorescent protein-expressing nude mice. The growth and metastasis of the tumors were visualized using a whole-body in vivo fluorescence imaging system in real time. HCC tissues were extracted from tumor-bearing mice, and cut into 5-µm serial frozen slices. The organizational structure of the transplanted tumors was observed under a microscope. A dual-color fluorescence tracing orthotopic transplantation tumor model of HCC was successfully established with a success rate of 100%. The growth and metastasis of the tumors were visualized at each stage of development in the tumor-bearing mice. Tumor cells with red fluorescence and host cells with green fluorescence were identified to merge in the reconstruction region of tumor tissue. The invasion, migration, and cell fusion between tumor and host cells was observed clearly. The dual-color fluorescence tracing ortho-topic transplantation model of HCC was determined to be a stable and reliable method for tracking tumor progression. Mutual interactions between hepatoma cells and host tissues may be observed directly using this model, further elucidating the development of the tumor microenvironment. PMID:26647736

  13. Effects of different mitogens on intrasplenic liver tissue transplants in comparison to orthotopic liver.

    PubMed

    Lupp, Amelie; Lucas, Norma; Tralls, Manuela; Fuchs, Udo; Danz, Manfred

    2003-06-01

    Ectopic liver cell transplants, when compared to orthotopic liver, can serve as a tool to study topic influences on liver cell differentiation, multiplication, function and responsiveness to xenobiotics. The aim of the present study was to evaluate, if characteristic effects of mitogens are exerted in both liver and intrasplenic liver cell transplants in a similar manner. Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic rats. Four months later, transplant recipients and controls were treated with fluorene (FEN), fluorenone (FON), 2-acetylaminofluorene (AAF), N-nitrosodibenzylamine (NDBA) or the solvent 48 hours before sacrifice. The following parameters were assessed within livers and spleens: mitotic activity of hepatocytes, glycogen content, cytochrome P450 (P450) isoforms expression, P450 mediated monooxygenase functions, tissue content of lipid peroxides (LPO) and of reduced and oxidized glutathione (GSH; GSSG). In both orthotopic livers and intrasplenic transplants FEN, FON or NDBA administration increased the mitotic activity of the hepatocytes. Treatment with the mitogens caused a distinct and characteristic induction of the P450 isoforms expression and of the respective monooxygenase functions in the livers and (with certain differences) also in the transplants. FEN and FON slightly increased, AAF and NDBA reduced liver glycogen content. The latter effect was also seen in the transplants. NDBA administration caused a slight increase in tissue LPO content in livers, but not in spleens. Additionally, AAF or NDBA treatment led to an elevation of liver (but not of spleen) GSH and GSSG concentrations. The results of the present investigation show that characteristic effects of mitogens on orthotopic liver occur with certain differences also in ectopic liver cell transplants.

  14. Does Previous Abdominal Surgery Alter the Outcome of Pediatric Patients Subjected to Orthotopic Liver Transplantation?

    PubMed Central

    CUERVAS-MONS, VALENTIN; RIMOLA, ANTONI; VAN THIEL, DAVID H.; GAVALER, JUDITH S.; SCHADE, ROBERT R.; STARZL, THOMAS E.

    2010-01-01

    The medical, anesthesia, and surgical records of 89 consecutive pediatric patients who underwent an orthotopic hepatic transplantation procedure at the University of Pittsburgh from February 1981 to May 1984 were reviewed to evaluate the effect of prior abdominal surgery upon the morbidity and mortality of orthotopic liver transplantation in children. Fifty-seven children (group 1) had had prior abdominal surgery, whereas 32 (group 2) had not. The group 1 subjects were younger (p < 0.001), had better prothrombin times (p < 0.01), and better platelet counts (p < 0.02) than did those in group 2. No difference in the duration of anesthesia or intra-operative use of fresh frozen plasma or platelets was evident between the two groups. However, group 1 patients were given more red blood cells intraoperatively than were the group 2 patients (p < 0.01). The group 1 patients had more total postoperative infections (p < 0.05), which was due solely to a greater number of abdominal infections (p < 0.05), but similar total hospital and intensive care unit stays as did the group 2 patients. When those in group 1 were divided into those having a previous Kasai procedure versus those who did not, no differences between the two groups were apparent except for age. Based upon these data, we conclude that prior abdominal surgery does not affect mortality, the duration of hospital or intensive care unit stay, plasma or platelet requirements, and total anesthesia time required for orthotopic liver transplantation, but does enhance the number of red blood cell transfusions and infections, particularly abdominal infections, in children undergoing this procedure. PMID:3512356

  15. Establishment of a dual-color fluorescence tracing orthotopic transplantation model of hepatocellular carcinoma.

    PubMed

    Chen, Qian; Wang, Xiaoping; Wu, Hao; Wang, Hui; Zhu, Mingao; Wang, Roushu; Wu, Ying; Zhang, Luyao; Meng, Qiao; Song, Ranran; Zhuang, Zhixiang; Huang, Qiang

    2016-01-01

    Different experimental models of hepatocellular carcinoma (HCC) have been used to investigate the biological mechanisms of hepatocarcinogenesis and its progression. However, previous studies have highlighted the difficulty of distinguishing between the tumor cells and stroma in experimental models of HCC. Therefore the aim of the present study was to establish a red‑green dual‑color fluorescence tracing orthotopic transplantation model of HCC, and investigate its practical values. Stable high red fluorescent protein (RFP)‑expressing HepG2 human hepatoma cells and Hepa1‑6 mice hepatoma cells were injected into the right liver lobe of green fluorescent protein‑expressing nude mice. The growth and metastasis of the tumors were visualized using a whole‑body in vivo fluorescence imaging system in real time. HCC tissues were extracted from tumor‑bearing mice, and cut into 5‑µm serial frozen slices. The organizational structure of the transplanted tumors was observed under a microscope. A dual‑color fluorescence tracing orthotopic transplantation tumor model of HCC was successfully established with a success rate of 100%. The growth and metastasis of the tumors were visualized at each stage of development in the tumor‑bearing mice. Tumor cells with red fluorescence and host cells with green fluorescence were identified to merge in the reconstruction region of tumor tissue. The invasion, migration, and cell fusion between tumor and host cells was observed clearly. The dual‑color fluorescence tracing orthotopic transplantation model of HCC was determined to be a stable and reliable method for tracking tumor progression. Mutual interactions between hepatoma cells and host tissues may be observed directly using this model, further elucidating the development of the tumor microenvironment.

  16. Orthotopic mouse models of tumor metastasis expressing fluorescent reporters produce imageable circulating tumor cells.

    PubMed

    Hoffman, Robert M

    2014-12-01

    Circulating tumor cells (CTC) are of high importance, since they are potential metastatic precursors and are readily available for prognostic analysis and treatment testing. In this review, we demonstrate the great power that green fluorescent protein (GFP) labeling and orthotopic mouse models of cancer confer to the study of CTCs for isolation and characterization, including metastatic testing in mice and the chick embryo as well as drug response testing in vitro. We also describe a facile method to label patient CTCs ex vivo using a telomerase-expressing GFP-containing adenovirus that will allow the CTC studies described in this review to be translated clinically.

  17. Orthotopic heart transplantation in two infants with histiocytoid cardiomyopathy and left ventricular non-compaction.

    PubMed

    Siehr, Stephanie L; Bernstein, Daniel; Yeh, Justin; Berry, Gerald J; Rosenthal, David N; Hollander, Seth A

    2013-11-01

    HC is a rare cause of congestive heart failure that typically presents with malignant ventricular arrhythmias in infants, often requiring urgent intervention. Successful heart transplantation in a patient with HC has only been reported once (J Heart Lung Transplant 2004: 23: 902). The combination of HC with concurrent LVNC has only been described three times (Int J Legal Med 2009: 123: 47; Hum Pathol 2005: 36: 403; Pediatr Dev Pathol 2012: 15: 397). We report two rare cases of HC with LVNC in two infants presenting with cardiogenic shock, one requiring ECMO support who was successfully bridged to orthotopic heart transplantation with a Berlin Heart LVAD.

  18. [Successful ablation of an atrioventricular nodal reentrant tachycardia ablation 2 years after orthotopic heart transplantation].

    PubMed

    Bellmann, Barbara; Reith, Sebastian; Gemein, Christopher; Schauerte, Patrick

    2015-09-01

    We report the case of a 48-year-old woman with an orthotopic heart transplantation. Two years after transplantation, the patient reported intermittent palpitations and dyspnea. The results of the 12-lead electrogram provided suspicion of AV nodal reentrant tachycardia (AVNRT), which was confirmed in the electrophysiological examination. The AVNRT was successfully eliminated without complications by radiofrequency catheter ablation of the slow pathway. The case shows that an AVNRT, even with existing sinus rhythm of the original heart, can also occur on the transplanted heart and ablation is safe and feasible. PMID:26208808

  19. [A new case of hepatic adenomatosis treated with orthotopic liver transplantation].

    PubMed

    Yunta, P J; Moya, A; San-Juan, F; López-Andújar, R; De Juan, M; Orbis, F; Mir, J

    2001-09-01

    Hepatic adenomatosis is a rare disease with multiple hepatic adenomas (10 or more), not associated with an history of oral contraceptive use or anabolic steroids use or with glycogen storage disease. A new case is reported in a 23 year-old woman who consulted for an abdominal mass and who had more than 50 adenomas of the liver. The suspicion of malignant transformation by the elevation of the alpha-foetoprotein, and the diffuse affectation of the liver, with minimum free parenchyma, suggested to carry out an orthotopic liver transplantation. The definitive histological examination of the surgical specimen confirmed the existence of local areas of hepatocellular carcinoma.

  20. Replacing a Missing Tooth

    MedlinePlus

    ... majority of patients with clefts will require full orthodontic treatment, especially if the cleft has passed through ... later replacement of the missing lateral incisor. During orthodontic treatment, an artificial tooth may be attached to ...

  1. Hormone Replacement Therapy

    MedlinePlus

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  2. Kidney Replacement Therapy

    MedlinePlus

    ... their function with either dialysis or a transplant. Dialysis Dialysis, the more common form of kidney-replacement ... the result of diabetes, not of hemodialysis. Peritoneal dialysis Another form of dialysis is called peritoneal dialysis. ...

  3. Artificial Disc Replacement

    MedlinePlus

    ... treat this condition, alternatives to disc replacement include fusion, nonoperative care or no treatment. Typically, surgery is ... operative treatment for disc pain has been spinal fusion. This is a surgical procedure in which disc ...

  4. Two-Year Experience of Orthotopic Liver Transplantation in Afzalipoor Hospital, Kerman, Southeastern Iran

    PubMed Central

    Dehghani, M.; Poorseidi, B.; Sattari, H.; Nikeghbalian, S.; Zahedi, M. J.; Seyyed-Mirzaei, S. M.; Shafiei, M.; Vahedian, M.; Malek-Hosseini, S. A.

    2012-01-01

    Background: End-stage liver diseases are common in Iran. The only therapeutic option for these patients is liver transplantation. Objective: To present our 2-year experience of liver transplantations in Afzalipoor Hospital, Kerman, southeastern Iran. Methods: From November 2009 to September 2011, 12 patients underwent orthotopic liver transplantation in our center. Their data including demographics, indications for transplantation, MELD scores, post-operative complications and their management were collected. Results: Patients (7 women and 5 men) aged between 14 and 55 years. Indications for the transplantation included HBV infection (n=5), cryptogenic cirrhosis (n=2), Wilson’s disease, alcoholism (n=1), HCV infection (n=1), Budd-Chiari syndrome (n=1), and autoimmune hepatitis (n=1). MELD score of patients ranged from 16 to 30. All patients received tacrolimus, mycophenolate mofetile and corticosteroid, postoperatively. 2 patients died of pulmonary and intra-abdominal infections with resultant to multiple organ failure. Nonfunctioning of transplanted liver and ongoing bleeding resulted in death in another patients. 9 patients are well doing and have excellent liver functions. Conclusion: We had relatively successful results in our experience of orthotopic liver transplantation. Vicinity of our center to Shiraz Transplant Center would be an important factor in this success. PMID:25013635

  5. Effect of treatment with baicalein on the intracerebral tumor growth and survival of orthotopic glioma models.

    PubMed

    Wang, Fu-Rong; Jiang, Yong-Sheng

    2015-08-01

    Baicalein, a widely used Chinese herbal medicine, has been proved as a promising chemopreventive compound for many cancers. The aim of this work was to assess the anti-tumor effect of baicalein in the orthotopic glioma models. It was found that treatment of mice with U87 gliomas with baicalein (20 and 40 mg/kg/day, i.p.) significantly inhibited the intracerebral tumor growth and prolonged the survival. Furthermore, treatment with baicalein suppressed cell proliferation, promoted apoptosis, and arrested cell cycle in U87 gliomas. In addition, treatment with baicalein reduced tumor permeability, attenuated edema of tumors and brains, and improved tight junctions in gliomas. Finally, treatment with baicalein reduced the expression of HIF-1α, VEGF, and VEGFR2 in U87 gliomas. In addition, treatment with baicalein also markedly suppressed tumor growth and prolonged the survival of rats with 9L gliomas. In conclusion, baicalein has an obvious anti-tumor activity in the orthotopic glioma models. Our results suggested that treatment with baicalein might be an effective therapy for recurrent malignant brain cancers through suppressing tumor growth and alleviating edema.

  6. An orthotopic mouse model of small cell lung cancer reflects the clinical course in patients.

    PubMed

    Taromi, Sanaz; Kayser, Gian; von Elverfeldt, Dominik; Reichardt, Wilfried; Braun, Friederike; Weber, Wolfgang A; Zeiser, Robert; Burger, Meike

    2016-10-01

    Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with very poor prognosis due to early metastatic spread and development of chemoresistance. In the last 30 years the study of SCLC has been constrained by a lack of primary human tumor specimen thus highlighting the need of a suitable mouse model. In this article we present the establishment of an orthotopic xenograft mouse model which accurately reproduced the clinical course of SCLC. Orthotopic implantation enabled engraftment of primary lung tumors in all injected mice. Furthermore, immunodeficiency of mice allowed formation of spontaneous metastases in characteristic organs. Bioluminescence Imaging, Magnetic Resonance Imaging and Positron emission tomography were applied to monitor engraftment, metabolism and the exact growth of tumors over time. In order to mimic the extensive disease stage, mice were injected with aggressive human chemoresistant cells leading to development of chemoresistant tumors and early metastatic spread. As a proof of concept treatment of tumor-bearing mice with conventional chemotherapeutics reduced tumor volumes, but a complete regression of tumors was not achieved. By mimicking the extensive disease stage our mouse model can facilitate the study of mechanisms contributing to chemoresistance and metastasis formation, as well as drug screening and evaluation of new treatment strategies for SCLC patients. PMID:27380917

  7. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus-Seropositive Patients.

    PubMed

    Conte, Antonio Hernandez; Kittleson, Michelle M; Dilibero, Deanna; Hardy, W David; Kobashigawa, Jon A; Esmailian, Fardad

    2016-02-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus-accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation.

  8. Serial orthotopic transplantation of epithelial tumors in single-cell suspension

    PubMed Central

    McCauley, Heather A.; Guasch, Géraldine

    2014-01-01

    Orthotopic transplantation of tumor tissue into recipient mice has long been established to study the role of the microenvironment in tumorigenesis and metastasis. Many of these transplantation assays involve the surgical implantation of an undissociated piece of tumor tissue. However, dissociation of tumor tissue into a single cell suspension prior to orthotopic transplantation enables the injection of fewer cell numbers, the selection of tumor-initiating populations by specific purification using antibody staining and fluorescence-activated cell sorting and the analysis of tumor-forming efficiency. In this chapter, we provide a method to perform serial transplantation of tumor cells into their niche of origin. Visualization of the location of transplanted tumor cells is essential to confirm the success of the transplant as well as the viability of transplanted cells. We also describe an optimized immunofluorescence protocol to visualize tumor cells shortly after transplantation. This serial transplantation protocol allows for an experimental tumorigenesis assay to more closely mimic spontaneous tumor formation and is applicable to many microenvironments. PMID:23959996

  9. Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model

    PubMed Central

    Chen, Xiaoyun; Wang, Jian; Cao, Ziquan; Hosaka, Kayoko; Jensen, Lasse; Yang, Huasheng; Sun, Yuping; Zhuang, Rujie; Liu, Yizhi; Cao, Yihai

    2015-01-01

    Retinoblastoma is a highly invasive malignant tumor that often invades the brain and metastasizes to distal organs through the blood stream. Invasiveness and metastasis of retinoblastoma can occur at the early stage of tumor development. However, an optimal preclinical model to study retinoblastoma invasiveness and metastasis in relation to drug treatment has not been developed. Here, we developed an orthotopic zebrafish model in which retinoblastoma invasion and metastasis can be monitored at a single cell level. We took the advantages of immune privilege and transparent nature of developing zebrafish embryos. Intravitreal implantation of color-coded retinoblastoma cells allowed us to kinetically monitor tumor cell invasion and metastasis. Further, interactions between retinoblastoma cells and surrounding microvasculatures were studied using a transgenic zebrafish that exhibited green fluorescent signals in blood vessels. We discovered that tumor cells invaded neighboring tissues and blood stream when primary tumors were at the microscopic sizes. These findings demonstrate that retinoblastoma metastasis occurs at the early stage and antiangiogenic drugs such as Vegf morpholino and sunitinib could potentially interfere with tumor invasiveness and metastasis. Thus, this orthotopic retinoblastoma model offers a new and unique opportunity to study the early events of tumor invasion, metastasis and drug responses. PMID:26169357

  10. The long-term fate of fresh and frozen orthotopic bone allografts in genetically defined rats.

    PubMed

    Bos, G D; Goldberg, V M; Gordon, N H; Dollinger, B M; Zika, J M; Powell, A E; Heiple, K G

    1985-01-01

    Fresh and frozen orthotopic iliac crest bone grafts in rats were studied histologically for determination of the long-term effects of histocompatibility matching and the freezing process on orthotopic bone graft incorporation. Grafts exchanged between groups of inbred rats, syngeneic or differing with respect to major or minor histocompatibility loci, were studied histologically at 20, 30, 40, 50, and 150 days after bone transplantation. A numerical histologic scoring system was developed and used by three observers for evaluation of coded hematoxylin and eosin sections. All frozen graft groups had the same fate regardless of histocompatibility relations between donors and recipients, and all grafts were inferior to fresh syngeneic grafts. Both fresh allograft groups received similar scores and initially at 20 and 30 days had scores similar to those of the fresh syngeneic groups. In the later intervals, however, the fresh allografts were inferior to the fresh syngeneic grafts and similar to the frozen groups. This is consistent with an older model describing two distinct phases of osteogenesis. In the long term, frozen syngeneic and fresh and frozen allografts across major and minor histocompatibility barriers were comparable, but all were significantly inferior to fresh syngeneic bone grafts.

  11. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours.

    PubMed

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Ora, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel

    2015-03-01

    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma.

  12. An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma

    PubMed Central

    Sasaki, Hiromi; Iyer, Swathi V.; Sasaki, Ken; Tawfik, Ossama W.; Iwakuma, Tomoo

    2015-01-01

    Osteosarcoma, the most common type of primary bone cancer, is the second highest cause of cancer-related death in pediatric patients. To understand the mechanisms behind osteosarcoma progression and to discover novel therapeutic strategies for this disease, a reliable and appropriate mouse model is essential. For this purpose, osteosarcoma cells need to be injected into the bone marrow. Previously, the intratibial and intrafemoral injection methods were reported; however, the major drawback of these methods is the potential leakage of tumor cells from the injection site during or after these procedures. To overcome this, we have established an improved method to minimize leakage in an orthotopic mouse model of osteosarcoma. By taking advantage of the anatomical benefits of the femur with less bowing and larger medullary cavity than those of the tibia, osteosarcoma cells are injected directly into the femoral cavity following reaming of its intramedullary space. To prevent potential leakage of tumor cells during and after the surgery, the injection site is sealed with bone wax. This method requires a minor surgery of approximately 15 minutes under anesthesia. Our established orthotopic osteosarcoma model could serve as a valuable and reliable tool for examining tumor progression of various types of bone tumors. PMID:26142221

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

    SciTech Connect

    Sochman, Jan; Peregrin, Jan H.; Pulda, Zdenek; Pavcnik, Dusan; Uchida, Barry T.; Timmermans, Hans A.; Roesch, Josef

    2010-04-15

    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 period 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.

  14. Orthotopic liver transplantation in fulminant and subfulminant hepatitis. The Paul Brousse experience.

    PubMed Central

    Bismuth, H; Samuel, D; Castaing, D; Adam, R; Saliba, F; Johann, M; Azoulay, D; Ducot, B; Chiche, L

    1995-01-01

    OBJECTIVE: The authors report on the experience of orthotopic liver transplantation in fulminant hepatitis at Paul Brousse Hospital. SUMMARY BACKGROUND DATA: Liver transplantation is a breakthrough in the treatment of patients with fulminant hepatitis. However, the indications, the timing for transplantation, the type of transplantation, and the use of ABO incompatible grafts in this setting still are debated. METHODS: Transplantation was indicated in patients with confusion or coma and factor V less than 20%, younger than 30 years of age, and confusion or coma and factor V less than 30% older than 30 years of age. RESULTS: Among 139 patients who met the aforementioned criteria for transplantation, 1 recovered, 22 died before transplantation, and 116 underwent transplants with a 1-year survival of 68%. Survival was 83% in patients with grade 1 and 2 comas at transplantation versus 56% (p < 0.001) in those with grade 3 comas; it was 51% versus 81% (p < 0.001) in those transplanted with high risk (ABO-incompatible, split, or steatotic) and low-risk grafts, respectively. In a multivariate analysis, steatotic and partial grafts were predictive of poorer patient survival, and ABO incompatibility was predictive of poorer graft survival. CONCLUSIONS: Orthotopic liver transplantation is an effective treatment in fulminant hepatitis. Use of high-risk grafts permitted transplantation of 83% of patients, but was responsible for higher mortality. PMID:7639578

  15. 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

  16. Orthotopic liver transplantation in critically ill cirrhotic patients with multi-organ failure: a single-center experience.

    PubMed

    Umgelter, A; Lange, K; Kornberg, A; Büchler, P; Friess, H; Schmid, R M

    2011-12-01

    Due to the lack of donor organs for orthotopic liver transplantation (OLT) in Germany, a larger proportion of patients advance to multi-organ failure (MOF) before OLT. Twenty-three patients on the waiting list for OLT were admitted to our intensive care unit (ICU) from January 2007 until September 2009. They consisted of 16 men and 7 women of median (25th-75th percentile) age of 60 years (54-65). Acute Physiology and Chronic Health Evaluation (APACHE II) score upon ICU admission was 26 (19-34); Model of End-Stage Liver Disease (MELD) score was 29 (22-41); Sequential Organ Failure Assessment (SOFA) score was 12 (8-16). The 90-day mortality rate was 39%. A decrease in MELD score during the first 48 hours (-2 [-5-0] vs 2 [-1-4]; P=.019) was associated with survival. Thirteen patients underwent transplantation from the ICU. By the time of the OLT, the MELD scores had deteriorated to 38 (33-39) and SOFA scores to 19 (18-19). All patients were mechanically ventilated and received hemodynamic support with catecholamines. Ten of 13 patients (77%) received renal replacement therapy and/or single pass albumin dialysis. Eight of 13 patients (62%) had a SOFA score of 3 or 4 (organ failure) in each of the respective subscores for the cardiovascular, renal, and respiratory systems at the time of OLT. The 90-day mortality rate after OLT was 38% and the 1-year-mortality rate was 54%. Patients who did not survive 90 days post OLT showed lower MELD scores on admission (33 [18-35] vs 44 [32-46]; P=.045), an increased MELD during the first 48 hours (3 [1-4] vs -2 [-8-1]; P=.002), and a longer ICU stay before OLT (32 [18-37] vs 8 [2-15]; P=.006). In conclusion, OLT may be successful treatment for cirrhotic patients with MOF. Outcomes of MOF in cirrhotic patients may improve after OLT but are generally worse than acceptable. A shorter ICU waiting time seemed to be beneficial.

  17. Toxicology of chlorofluorocarbon replacements.

    PubMed Central

    Dekant, W

    1996-01-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements. PMID:8722112

  18. Toxicology of chlorofluorocarbon replacements.

    PubMed

    Dekant, W

    1996-03-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements.

  19. Triple Starr Valve Replacement

    PubMed Central

    Braimbridge, M. V.; Clement, A. J.; Brown, A. Hedley; Sabar, E.; Mendel, D.

    1969-01-01

    Of nine patients who have had triple valve replacements for organic rheumatic triple valve disease two died in the postoperative period from inadequate myocardial reserve, and a third died four months later from cerebral embolism originating from clot on the left atrial wall. The remainder are well and, except for one, leading normal lives. Though cardiac transplantation has been recommended and used successfully for triple valve disease by Cooley, it is suggested that the long-term outlook today of triple valve replacement is likely to be better than that of transplantation. ImagesFig. 1Fig. 2Fig. 3 PMID:5809243

  20. Line Replaceable Unit Analysis

    NASA Technical Reports Server (NTRS)

    Oepomo, T.; Prouty, T. V.

    1982-01-01

    Shuttle LRU (Line Replaceable Unit) Analysis Program (SLAP) aids in evaluation of LRU interface voltages in Shuttle orbiter electrical system. Slap includes reduced model of Shuttle LRU circuit. Although primarily intended for analysis of Shuttle LRU's SLAP could be adapted for voltage analysis in other situations.

  1. 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…

  2. Python import replacement

    SciTech Connect

    2011-10-01

    SmartImport.py is a Python source-code file that implements a replacement for the standard Python module importer. The code is derived from knee.py, a file in the standard Python diestribution , and adds functionality to improve the performance of Python module imports in massively parallel contexts.

  3. 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.

  4. Clinical features and treatment of Malassezia folliculitis with fluconazole in orthotopic heart transplant recipients.

    PubMed

    Rhie, S; Turcios, R; Buckley, H; Suh, B

    2000-02-01

    Orthotopic heart transplant recipients need immunosuppressive treatment and are at an increased risk for opportunistic infections such as Malassezia folliculitis. During a 4-month period (July to October 1990), 11 such cases were identified and treated; all were male with mean age of 43+/-9 years and on standard triple immunosuppressive therapy. Skin scrapings in potassium hydroxide (KOH) preparation with microscopy and/or culture identified either Malassezia furfur or Malassezia pachydermatis as the etiologic agent. A treatment with topical preparation (clotrimazole 1% and selenium sulfide lotion) was effective in 6 patients, whereas the rest received systemic fluconazole treatment with satisfactory outcome; all lesions were resolved within 3 weeks. Fluconazole appears to be an effective agent with excellent therapeutic outcome when administered for 3 weeks.

  5. Life-Threatening Cardiac Tamponade Secondary to Chylopericardium Following Orthotopic Heart Transplantation—A Case Report

    PubMed Central

    Wierzbicki, Karol; We˛grzyn, Piotr; Kapelak, Bogusław

    2015-01-01

    Chylopericardium is a rare complication in cardiac surgery, and an extremely rare occurrence in patients following orthotopic heart transplantation (OHT), which, however, can lead to cardiac tamponade. Here we present a case of a 59-year-old man who underwent OHT and suffered from chylopericardium resulting in cardiac tamponade late in the postoperative course, despite the initially uneventful early postoperative period (decreasing blood drainage was observed directly after the procedure, and the drains were safely removed). After the diagnosis of chylopericardium was made, the conservative treatment was initiated, which turned out to be insufficient, and eventually invasive approach for the recurrence of tamponade secondary to chylopericardium was required. We discuss the available therapeutic options for chylopericardium and demonstrate the successful invasive therapeutic approach with use of the absorbable fibrin sealant patch. PMID:26548537

  6. A quantitative model to predict blood use in adult orthotopic liver transplantation.

    PubMed

    Liu, Chang; Vachharajani, Neeta; Song, Shuang; Cooke, Rhonda; Kangrga, Ivan; Chapman, William C; Grossman, Brenda J

    2015-12-01

    To identify preoperative predictors for the use of any blood component during and after orthotopic liver transplantation (OLT), we performed a retrospective analysis on 602 OLT patients who were randomly split into a training set (n = 482) and a validation set (n = 120). Hemoglobin and calculated MELD score were identified as independent predictors for blood use using bootstrap aggregation. A logistic regression model constructed using both variables showed comparable performance in the training and validation sets. Predictive scores can be obtained from a nomogram, and a score above -2.328 predicted transfusion of any blood component with a positive predictive value of 97% and 96% in the training and validation sets, respectively. PMID:26297190

  7. Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy.

    PubMed Central

    Turner, J. H.; Rose, A. H.; Glancy, R. J.; Penhale, W. J.

    1998-01-01

    Extrapolation to humans from experimental radioimmunotherapy in nude mouse xenograft models is confounded by large relative tumour size and small volume of distribution in mice allowing tumour uptake of radiolabelled antibodies unattainable in patients. Our large animal model of human tumours in cyclosporin-immunosuppressed sheep demonstrated tumour uptake of targeted radiolabelled monoclonal antibodies comparable with uptakes reported in clinical trials. Sheep immunosuppression with daily intravenous cyclosporin augmented by oral ketoconazole maintained trough blood levels of cyclosporin within the range 1000-1500 ng ml(-1). Human tumour cells were transplanted orthotopically by inoculation of 10(7) cells: SKMEL melanoma subcutaneously; LS174T and HT29 colon carcinoma into bowel, peritoneum and liver; and JAM ovarian carcinoma into ovary and peritoneum. Tumour xenografts grew at all sites within 3 weeks of inoculation, preserving characteristic morphology without evidence of necrosis or host rejection. Lymphatic metastasis was demonstrated in regional nodes draining xenografts of melanoma and ovarian carcinoma. Colonic LS1 74T xenografts produced mucin and carcinoembryonic antigen (CEA). The anti-CEA IgG1 monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% DI g(-1) (percentage of injected dose per gram) and 0.034% DI g(-1) in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% DI g(-1). Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy. Images Figure 1 Figure 2 Figure 3 PMID:9716032

  8. Characterization of a novel transplantable orthotopic rat bladder transitional cell tumour model.

    PubMed

    Xiao, Z; McCallum, T J; Brown, K M; Miller, G G; Halls, S B; Parney, I; Moore, R B

    1999-10-01

    An animal tumour model that mimics the human counterpart is essential for preclinical evaluation of new treatment modalities. The objective of this study was to develop and characterize such a model. To accomplish this, the established AY-27 rat bladder transitional cell carcinoma (TCC) cell line was transplanted orthotopically into Fischer CDF344 female rats. AY-27 TCC cells were grown in monolayer cell culture and instilled intravesically as single cell suspensions into bladders that had been conditioned with mild acid washing. Tumour growth was assessed weekly by subjecting the rats to magnetic resonance imaging (MRI). At intervals following implantation and MRI tumour detection, the animals were sacrificed for necropsy, histological examination and immunocytochemical studies. Flow cytometry was also performed for detection of Fas or Fas-ligand expression on AY-27 cells. The overall tumour establishment was 95% (97/102 rats) at 12-50 days, while in a subgroup of animals sacrificed at 16 days, 80 out of 82 animals (97%) developed TCC, the majority of which was superficial. Tumour stage was assessed by gross pathology and light microscopy. Histological examination of the tumour specimens confirmed the presence of grade II-III TCC. Immunocytochemistry confirmed that the tumour model maintained the features of TCC. The changes seen on MRI correlated well with the extent of tumour invasion identified histologically. Patchy carcinoma in situ could be detected histologically 12-13 days post-inoculation, and progressed to papillary tumour or invasive disease thereafter. Neither Fas nor Fas-ligand was expressed on AY-27 cells. The orthotopic AY-27 TCC model is highly reproducible and is ideal for preclinical studies on experimental intravesical therapies.

  9. SERPINI1 regulates epithelial-mesenchymal transition in an orthotopic implantation model of colorectal cancer.

    PubMed

    Matsuda, Yasufumi; Miura, Koh; Yamane, Junko; Shima, Hiroshi; Fujibuchi, Wataru; Ishida, Kazuyuki; Fujishima, Fumiyoshi; Ohnuma, Shinobu; Sasaki, Hiroyuki; Nagao, Munenori; Tanaka, Naoki; Satoh, Kennichi; Naitoh, Takeshi; Unno, Michiaki

    2016-05-01

    An increasingly accepted concept is that the progression of colorectal cancer is accompanied by epithelial-mesenchymal transition (EMT). In our study, in order to characterize the properties of EMT in 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumors in vivo, as well as cells cultured in vitro, were immunostained for EMT markers. The immunostaining revealed that seven of the cells had an epithelial phenotype with a high expression of E-cadherin, whereas other cells showed opposite patterns, such as a high expression of vimentin (CX-1, COLO205, CloneA, HCT116, and SW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480, SW620, and COLO320). We evaluated these findings in combination with microarray analyses, and selected five genes: CHST11, SERPINI1, AGR2, FBP1, and FOXA1. Next, we downregulated the expression of SERPINI1 with siRNA in the cells, the results of which showed reverse-EMT changes at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secreted SERPINI1 protein of SW620 cells, which supported the importance of SERPINI1 in EMT. The development of therapeutic strategies targeting EMT is ongoing, including methods targeting the transforming growth factor-β signaling pathway as well as the Wnt pathway. SERPINI1 is an important regulator of EMT. Our findings help to elucidate the signaling pathways of EMT, hopefully clarifying therapeutic pathways as well. PMID:26892864

  10. Gasless minimum incision access used for extracorporeal orthotopic bladder substitution after laparoscopic radical cystectomy

    PubMed Central

    Tabakov, Alexey; Egosin, Alexander; Shakirov, Rustam; Mihailovskiy, Oleg; Bashirov, Valeriy

    2014-01-01

    Introduction Radical cystectomy is the gold standard for treating invasive bladder cancer. We report our outcomes of gasless minimum incision access (GMIA) for extracorporeal orthotopic bladder substitution (ECOBS) after laparoscopic radical cystectomy. Material and methods Radical surgery was performed in patients in the same hospital suffering from bladder cancer in T2N0M0 G1–2 stage. Group 1 included 11 patients aged 56.6 (42–72) years, which underwent laparoscopic radical cystectomy and ECOBS using GMIA. Group 2 included 18 patients aged 56.7 (41–76) years, which were operated by open radical cystectomy and orthotopic bladder substitution. Results The average duration of operation was 492.0 ±85.7 minutes in Group 1 and 318.0 ±58.0 in Group 2 (p = 0.001). Estimated blood loss was 290.0 ±120.0 and 613.2 ±359.0 ml in groups respectively. In the postoperative period, narcotic analgesics were used in the amount of 166.0 ±28.0 mg and 264.0 ±112.0 mg (p = 0.05), intestinal function recovery was observed on 3.5 ±0.9 and 6.0 ±2.9 days after the operation (p = 0.05) in the groups respectively. Minor postoperative complications were observed in 36.4% and 56.0%, major complications – in 9.1% and 11.2% in groups respectively. Median hospitalization time was 19.0 ±2.0 days in Group 1 and 24.9 ±6.5 in Group 2 (p = 0.01). Conclusions GMIA in ECOBS can be used as an effective surgical approach after laparoscopic radical cystectomy; this method requires further observation. PMID:25247092

  11. 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

  12. 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.

  13. BDNF signaling contributes to oral cancer pain in a preclinical orthotopic rodent model

    PubMed Central

    Chodroff, Leah; Bendele, Michelle; Valenzuela, Vanessa; Henry, Michael

    2016-01-01

    The majority of patients with oral cancer report intense pain that is only partially managed by current analgesics. Thus, there is a strong need to study mechanisms as well as develop novel analgesics for oral cancer pain. Current study employed an orthotopic tongue cancer model with molecular and non-reflexive behavioral assays to determine possible mechanisms of oral cancer pain. Human oral squamous cell carcinoma cells line, HSC2, was injected into the tongue of male athymic mice and tumor growth was observed by day 6. Immunohistological analyses revealed a well-differentiated tumor with a localized immune response and pronounced sensory and sympathetic innervation and vascularization. The tumor expressed TMPRSS2, a protein previously reported with oral squamous cell carcinoma. ATF3 expression in trigeminal ganglia was not altered by tumor growth. Molecular characterization of the model demonstrated altered expression of several pain-related genes, out of which up-regulation of BDNF was most striking. Moreover, BDNF protein expression in trigeminal ganglia neurons was increased and inhibition of BDNF signaling with a tyrosine kinase B antagonist, ANA-12, reversed pain-like behaviors induced by the oral tumor. Oral squamous cell carcinoma tumor growth was also associated with a reduction in feeding, mechanical hypersensitivity in the face, as well as spontaneous pain behaviors as measured by the conditioned place preference test, all of which were reversed by analgesics. Interestingly, injection of HSC2 into the hindpaw did not reproduce this spectrum of pain behaviors; nor did injection of a colonic cancer cell line into the tongue. Taken together, this orthotopic oral cancer pain model reproduces the spectrum of pain reported by oral cancer patients, including higher order cognitive changes, and demonstrates that BDNF signaling constitutes a novel mechanism by which oral squamous cell carcinoma induces pain. Identification of the key role of tyrosine kinase B

  14. Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development

    PubMed Central

    Corson, Timothy W.; Samuels, Brian C.; Wenzel, Andrea A.; Geary, Anna J.; Riley, Amanda A.; McCarthy, Brian P.; Hanenberg, Helmut; Bailey, Barbara J.; Rogers, Pamela I.; Pollok, Karen E.; Rajashekhar, Gangaraju; Territo, Paul R.

    2014-01-01

    Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux () through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed , as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future. PMID:24901248

  15. Circulating tumor cells exhibit stem cell characteristics in an orthotopic mouse model of colorectal cancer

    PubMed Central

    Niemietz, Thomas; Betzler, Alexander M.; Nanduri, Lahiri K.; Bork, Ulrich; Kahlert, Christoph; Thepkaysone, May-Linn; Swiersy, Anka; Büchler, Markus W.; Reissfelder, Christoph; Weitz, Jürgen; Rahbari, Nuh N.

    2016-01-01

    The prognosis of colorectal cancer (CRC) is closely linked to the occurrence of distant metastases, which putatively develop from circulating tumor cells (CTCs) shed into circulation by the tumor. As far more CTCs are shed than eventually metastases develop, only a small subfraction of CTCs harbor full tumorigenic potential. The aim of this study was to further characterize CRC-derived CTCs to eventually identify the clinically relevant subfraction of CTCs. We established an orthotopic mouse model of CRC which reliably develops metastases and CTCs. We were able to culture the resulting CTCs in vitro, and demonstrated their tumor-forming capacity when re-injected into mice. The CTCs were then subjected to qPCR expression profiling, revealing downregulation of epithelial and proliferation markers. Genes associated with cell-cell adhesion (claudin-7, CD166) were significantly downregulated, indicating a more metastatic phenotype of CTCs compared to bulk tumor cells derived from hepatic metastases. The stem cell markers DLG7 and BMI1 were significantly upregulated in CTC, indicating a stem cell-like phenotype and increased capacity of tumor formation and self-renewal. In concert with their in vitro and in vivo tumorigenicity, these findings indicate stem cell properties of mouse-derived CTCs. In conclusion, we developed an orthotopic mouse model of CRC recapitulating the process of CRC dissemination. CTCs derived from this model exhibit stem-cell like characteristics and are able to form colonies in vitro and tumors in vivo. Our results provide new insight into the biology of CRC-derived CTCs and may provide new therapeutic targets in the metastatic cascade of CRC. PMID:27029058

  16. Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.

    PubMed

    Corson, Timothy W; Samuels, Brian C; Wenzel, Andrea A; Geary, Anna J; Riley, Amanda A; McCarthy, Brian P; Hanenberg, Helmut; Bailey, Barbara J; Rogers, Pamela I; Pollok, Karen E; Rajashekhar, Gangaraju; Territo, Paul R

    2014-01-01

    Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux ([Formula: see text]) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed [Formula: see text], as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, [Formula: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Formula: see text] modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future. PMID:24901248

  17. 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.

  18. Celotex (Registered) Replacement Study

    SciTech Connect

    Couture, S; Hafner, R

    2002-10-01

    The AL-R8 is the pit storage container in most widespread use at Pantex. The AL-R8 container family consists of standard 20-in.-diameter steel drums, 30 to 60 in. in height, with insulation inserts made of Celotex{reg_sign}--a fiberboard product made from processed sugar cane. Celotex is an acceptable material for inserts in many radioactive material shipping and storage containers. It is a good shock mitigator/insulator, does a fair job in fire protection (when oxygen is excluded), shielding, and criticality, and is inexpensive and easily available. However, the fiberboard absorbs water in humid environments which, when combined with chemical residues in the fiberboard, forms corrosive compounds that can shorten the life of the container and affect container contents. To protect the contents from this potentially damaging environment, the AL-R8 SI was developed to isolate the contents within a sealed stainless steel vessel inside the AL-R8. Although the SI protected the contents, corrosion studies indicated the SI lid bolts might corrode over time and surveillance showed that areas of the outer drum were still subject to corrosion. To address this potential problem, DOE/Albuquerque sponsored bolt and Celotex replacement studies. The bolt replacement study was assigned to Mason and Hanger's Pantex Facility and this Celotex Replacement Study to Lawrence Livermore National Laboratory. The Celotex Replacement Study evaluated options for replacing Celotex with a material that is chemically compatible with the AL-R8 SI container. The evaluation was limited to materials either used previously in nuclear materials shipping and storage containers or materials with known properties in a low-radiation environment. This limitation was set to ensure that the long-term aging effect on the new material is known a priori. Initial material evaluations narrowed the material choices to foam and cork. Although cork performed better than foam in some tests, cork was considered a less

  19. NARC Rayon Replacement Program

    NASA Technical Reports Server (NTRS)

    Wilson, Kenneth P.; McCool, Alex (Technical Monitor)

    2002-01-01

    This viewgraph presentation provides information on the search for a replacement product for the aerospace grade rayon formerly used in the reusable solid rocket motor (RSRM). The rayon used in RSRMs is no longer produced by the North American Rayon Corporation (NARC), though NASA has stockpiled rayon to be used until a suitable replacement is found to be used in the RSRM nozzle carbon cloth phenolic (CCP). The primary considerations are performance, process ability, variability, long term availability, and cost. The preference will be given to commercial off-the-shelf products as opposed to those which are custom made. The candidate materials have been tested in previous phases of this selection process, and Enka Textile Rayon has emerged as a possible fabric, though its availability is still in question.

  20. Total femoral replacement.

    PubMed

    Nerubay, J; Katznelson, A; Tichler, T; Rubinstein, Z; Morag, B; Bubis, J J

    1988-04-01

    Between 1973 and 1983, 19 patients with sarcoma of the femur were treated by adjuvant chemotherapy, excision of the entire femur, and replacement by a total femoral prosthesis. Five patients had excellent and nine had good functional results. Twelve patients died an average of 23 months after the procedure and seven are at present disease free. This limb-saving procedure permits rapid rehabilitation, prevents severe psychological problems, and improves the quality of life.

  1. Renal Replacement Therapy

    PubMed Central

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology. PMID:26918174

  2. Renal Replacement Therapy.

    PubMed

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients' clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the "Tower of Babel" of critical care nephrology. PMID:26918174

  3. Real-Time GFP Intravital Imaging of the Differences in Cellular and Angiogenic Behavior of Subcutaneous and Orthotopic Nude-Mouse Models of Human PC-3 Prostate Cancer.

    PubMed

    Zhang, Yong; Toneri, Makoto; Ma, Huaiyu; Yang, Zhijian; Bouvet, Michael; Goto, Yusuke; Seki, Naohiko; Hoffman, Robert M

    2016-11-01

    There are two major types of mouse xenograft models of cancer: subcutaneous implantation and orthotopic implantation. Subcutaneous transplant models are widely used with both cancer cell lines and human-tumor specimens. Recently, subcutaneous models of patient tumors, termed patient-derived xenographs (PDX) have become highly popular and have acquired such names as "Avatar" and "Xenopatients." However, such s.c. models rarely metastasize and are therefore not patient-like. In contrast, orthotopic models have the capability to metastasize. If intact fragments of tumor tissue are implanted by surgical orthotopic implantation (SOI), the metastatic potential can match that of the donor patient. The present study images in real time, using green fluorescent protein (GFP) expression, the very different tumor behavior at the orthotopic and subcutaneous sites of human prostate cancer PC-3 in athymic nude mice. By day-2 after tumor implantation, the orthotopic tumor is already highly vascularized and the cancer cells have begun to migrate out of the tumor. In contrast, the subcutaneous tumor only begins to be vascularized by day-3 and cells do not migrate from the tumor. Angiogenesis is much more extensive in the orthotopic tumor throughout the 2-week observation period. The orthotopic PC-3-GFP tumor progresses very rapidly and distinct metastasis have appeared in lymph nodes by day-3 which rapidly appear in many areas of the abdominal cavity including portal lymph nodes by day-7. At day-14, no invasion or metastasis was observed with the s.c. tumor even when the animal was extensively explored. These results explain why orthotopic tumors mimimc clinical metastatic tumors in nude mice and why subcutaneous tumors do not. J. Cell. Biochem. 117: 2546-2551, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012365

  4. Real-Time GFP Intravital Imaging of the Differences in Cellular and Angiogenic Behavior of Subcutaneous and Orthotopic Nude-Mouse Models of Human PC-3 Prostate Cancer.

    PubMed

    Zhang, Yong; Toneri, Makoto; Ma, Huaiyu; Yang, Zhijian; Bouvet, Michael; Goto, Yusuke; Seki, Naohiko; Hoffman, Robert M

    2016-11-01

    There are two major types of mouse xenograft models of cancer: subcutaneous implantation and orthotopic implantation. Subcutaneous transplant models are widely used with both cancer cell lines and human-tumor specimens. Recently, subcutaneous models of patient tumors, termed patient-derived xenographs (PDX) have become highly popular and have acquired such names as "Avatar" and "Xenopatients." However, such s.c. models rarely metastasize and are therefore not patient-like. In contrast, orthotopic models have the capability to metastasize. If intact fragments of tumor tissue are implanted by surgical orthotopic implantation (SOI), the metastatic potential can match that of the donor patient. The present study images in real time, using green fluorescent protein (GFP) expression, the very different tumor behavior at the orthotopic and subcutaneous sites of human prostate cancer PC-3 in athymic nude mice. By day-2 after tumor implantation, the orthotopic tumor is already highly vascularized and the cancer cells have begun to migrate out of the tumor. In contrast, the subcutaneous tumor only begins to be vascularized by day-3 and cells do not migrate from the tumor. Angiogenesis is much more extensive in the orthotopic tumor throughout the 2-week observation period. The orthotopic PC-3-GFP tumor progresses very rapidly and distinct metastasis have appeared in lymph nodes by day-3 which rapidly appear in many areas of the abdominal cavity including portal lymph nodes by day-7. At day-14, no invasion or metastasis was observed with the s.c. tumor even when the animal was extensively explored. These results explain why orthotopic tumors mimimc clinical metastatic tumors in nude mice and why subcutaneous tumors do not. J. Cell. Biochem. 117: 2546-2551, 2016. © 2016 Wiley Periodicals, Inc.

  5. Reflections on replacement.

    PubMed

    Ryder, N B

    1993-01-01

    In the United States, the total fertility rate is about 1.9 births per woman, down from a peak of 3.2 a generation ago and below the replacement level of 2.1 children. The proportion of women who will never have children has risen from 8% a generation ago to approximately 18% in 1993. The increase in the proportion of women in the labor force, a proximate explanation of the recent decline in intended fertility, is expected to continue. The demographic consequence is declining population with an older age structure. A pronatalist policy to alleviate this outcome, through monetary transfers from taxpayers to potential parents, is not only unlikely to succeed, it is politically unfeasible. An alternative solution, immediately effective but politically unpalatable, would be a generous immigration policy. Even with replacement level fertility, the population is destined to become much older. This inevitable aging of the population should be countered by appropriate institutional transformations: 1) with lower fertility, a larger proportion of women will be available to participate in the labor force to generate taxes needed to support a larger number of pensioners; 2) the institutional practice of ascribing a dependent status to anyone above a particular age can be changed; 3) concerns that an older labor force will have an obsolete education (and fewer years of it) can be countered by changing access to education. Yet, the most serious question is not merely the net reproduction rate, but producing adequate numbers of new adult citizens with responsibility and technical training in the modern world. The fundamental process of socializing children may be jeopardized by replacing the full-time parent with the hired care-giver, the peer group, and the television set. The attenuation of the bonds between parent and child may devalue the worth of childbearing itself. These portentous consequences deserve consideration. PMID:8313953

  6. Total ankle joint replacement.

    PubMed

    2016-02-01

    Ankle arthritis results in a stiff and painful ankle and can be a major cause of disability. For people with end-stage ankle arthritis, arthrodesis (ankle fusion) is effective at reducing pain in the shorter term, but results in a fixed joint, and over time the loss of mobility places stress on other joints in the foot that may lead to arthritis, pain and dysfunction. Another option is to perform a total ankle joint replacement, with the aim of giving the patient a mobile and pain-free ankle. In this article we review the efficacy of this procedure, including how it compares to ankle arthrodesis, and consider the indications and complications.

  7. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.

    PubMed

    Zhang, Changsong; Yang, Guangshun; Lu, Dewen; Ling, Yang; Chen, Guihua; Zhou, Tianbao

    2014-08-01

    The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; P<0.01). In addition, the numbers of cells in the liver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (P<0.0001). Furthermore, the numbers of cells positive for VEGF and bFGF expression in the spleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (P<0.01). VEGF and bFGF mRNA expression levels were also increased from 1 day following the surgery and reached a peak at day 3, prior to declining gradually and remaining at a relatively high level. VEGF and bFGF mRNA expression levels changed dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.

  8. Targeted Non-invasive Imaging of EGFR-expressing Orthotopic Pancreatic Cancer using Multispectral Optoacoustic Tomography (MSOT)

    PubMed Central

    Hudson, Shanice V.; Huang, Justin S.; Yin, Wenyuan; Albeituni, Sabrin; Rush, Jamie; Khanal, Anil; Yan, Jun; Ceresa, Brian P.; Frieboes, Hermann B.; McNally, Lacey R.

    2014-01-01

    Detection of orthotopic xenograft tumors is difficult due to poor spatial resolution and reduced image fidelity with traditional optical imaging modalities. In particular, light scattering and attenuation in tissue at depths beyond subcutaneous implantation hinder adequate visualization. We evaluate the use of multispectral optoacoustic tomography (MSOT) to detect upregulated epidermal growth factor (EGF) receptor in orthotopic pancreatic xenografts using a near-infrared (NIR) EGF-conjugated CF-750 fluorescent probe. MSOT is based on the photoacoustic effect and thus not limited by photon scattering, resulting in high-resolution tomographic images. Pancreatic tumor-bearing mice with luciferase-transduced S2VP10L tumors were intravenously injected with EGF-750 probe prior to MSOT imaging. We characterized probe specificity and bioactivity via immunoblotting, immunocytochemistry, and flow cytometric analysis. In vitro data along with optical bioluminescence/fluorescence imaging were used to validate acquired MSOT in vivo images of probe biodistribution. Indocyanine green dye was used as a non-specific control to define specificity of EGF-probe accumulation. Maximum accumulation occurred at six hours post-injection, demonstrating specific intra-tumoral probe uptake and minimal liver and kidney off-target accumulation. Optical bioluminescence and fluorescence imaging confirmed tumor-specific probe accumulation consistent with MSOT images. These studies demonstrate the utility of MSOT to obtain volumetric images of ligand probe biodistribution in vivo to detect orthotopic pancreatic tumor lesions through active targeting of EGF receptor. PMID:25217521

  9. Non-invasive fluorescent-protein imaging of orthotopic pancreatic-cancer-patient tumorgraft progression in nude mice.

    PubMed

    Suetsugu, Atsushi; Katz, Matthew; Fleming, Jason; Truty, Mark; Thomas, Ryan; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

    2012-08-01

    In order to individualize and therefore have more effective treatment for pancreatic cancer, we have developed a multicolor, imageable, orthotopic mouse model for individual patients with pancreatic cancer by passaging their tumors through transgenic nude mice expressing green fluorescent protein (GFP) and red fluorescent protein (RFP). The tumors acquired brightly fluorescent stroma from the transgenic host mice, which was stably associated with the tumors through multiple passages. In the present study, pancreatic cancer patient tumor specimens were initially established in NOD.CB17-Prkdc(scid)/NcrCrl (NOD/SCID) mice. The tumors were then passaged orthotopically into transgenic nude mice ubiquitously expressing GFP and subsequently to nude mice ubiquitously expressing RFP. The tumors, with very bright GFP and RFP stroma, were then orthotopically passaged to non-transgenic nude mice. It was possible to image the brightly fluorescent tumors non-invasively longitudinally as they progressed in the non-transgenic nude mice. This non-invasive imageable tumorgraft model will be valuable to screen for effective treatment options for individual patients with pancreatic cancer, as well as for the discovery of improved agents for this treatment-resistant disease.

  10. Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours

    PubMed Central

    Steen, Stig; Paskevicius, Audrius; Liao, Qiuming; Sjöberg, Trygve

    2016-01-01

    Abstract Objectives. The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24 hours after brain death and preserved for 24 hours before transplantation. Design. Circulatory normalization of brain dead (decapitated) pigs was obtained using a new pharmacological regimen (n = 10). The donor hearts were perfused at 8 °C in cycles of 15 min perfusion followed by 60 min without perfusion. The perfusate consisted of an albumin-containing hyperoncotic cardioplegic nutrition solution with hormones and erythrocytes. Orthotopic transplantation was done in 10 recipient pigs after 24 hours’ preservation. Transplanted pigs were monitored for 24 hours, then an adrenaline stress test was done. Results. All transplanted pigs were stable throughout the 24-hour observation period with mean aortic pressure around 80 mmHg and normal urine production. Mean right and left atrial pressures were in the range of 3–6 and 5–10 mmHg, respectively. Blood gases at 24 hours did not differ from baseline values. The adrenaline test showed a dose dependent response, with aortic pressure increasing from 98/70 to 220/150 mmHg and heart rate from 110 to 185 beats/min. Conclusion. Orthotopic transplantation of porcine hearts harvested 24 hours after brain death and preserved for 24 hours can be done safely. PMID:26882241

  11. Power Plant Replacement Study

    SciTech Connect

    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 be 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.

  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. Sutureless aortic valve replacement

    PubMed Central

    Phan, Kevin

    2015-01-01

    The increasing incidence of aortic stenosis and greater co-morbidities and risk profiles of the contemporary patient population has driven the development of minimally invasive aortic valve surgery and percutaneous transcatheter aortic valve implantation (TAVI) techniques to reduce surgical trauma. Recent technological developments have led to an alternative minimally invasive option which avoids the placement and tying of sutures, known as “sutureless” or rapid deployment aortic valves. Potential advantages for sutureless aortic prostheses include reducing cross-clamp and cardiopulmonary bypass (CPB) duration, facilitating minimally invasive surgery and complex cardiac interventions, whilst maintaining satisfactory hemodynamic outcomes and low paravalvular leak rates. However, given its recent developments, the majority of evidence regarding sutureless aortic valve replacement (SU-AVR) is limited to observational studies and there is a paucity of adequately-powered randomized studies. Recently, the International Valvular Surgery Study Group (IVSSG) has formulated to conduct the Sutureless Projects, set to be the largest international collaborative group to investigate this technology. This keynote lecture will overview the use, the potential advantages, the caveats, and current evidence of sutureless and rapid deployment aortic valve replacement (AVR). PMID:25870807

  14. Power Plant Replacement Study

    SciTech Connect

    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 be 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.

  15. Power Plant Replacement Study

    SciTech Connect

    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 be 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.

  16. Total disc replacement.

    PubMed

    Vital, J-M; Boissière, L

    2014-02-01

    Total disc replacement (TDR) (partial disc replacement will not be described) has been used in the lumbar spine since the 1980s, and more recently in the cervical spine. Although the biomechanical concepts are the same and both are inserted through an anterior approach, lumbar TDR is conventionally indicated for chronic low back pain, whereas cervical TDR is used for soft discal hernia resulting in cervicobrachial neuralgia. The insertion technique must be rigorous, with precise centering in the disc space, taking account of vascular anatomy, which is more complex in the lumbar region, particularly proximally to L5-S1. All of the numerous studies, including prospective randomized comparative trials, have demonstrated non-inferiority to fusion, or even short-term superiority regarding speed of improvement. The main implant-related complication is bridging heterotopic ossification with resulting loss of range of motion and increased rates of adjacent segment degeneration, although with an incidence lower than after arthrodesis. A sufficiently long follow-up, which has not yet been reached, will be necessary to establish definitively an advantage for TDR, particularly in the cervical spine. PMID:24412045

  17. Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas.

    PubMed

    Wei, J; Wahl, J; Nakamura, T; Stiller, D; Mertens, T; Debatin, K-M; Beltinger, C

    2007-11-01

    Malignant gliomas remain largely incurable despite intensive efforts to develop novel therapies. Replicating oncolytic viruses have shown great promise, among them attenuated measles viruses of the Edmonston B strain (MV-Edm). However, host immune response and the infiltrative nature of gliomas limit their efficacy. We show that human blood outgrowth endothelial cells (BOECs), readily expandable from peripheral blood, are easily infected by MV-Edm and allow replication of MV-Edm while surviving long enough after infection to serve as vehicles for MV-Edm (BOEC/MV-Edm). After intravenous and peritumoral injection, BOEC/MV-Edm deliver the viruses selectively to irradiated orthotopic U87 gliomas in mice. At the tumor, MV-Edm produced by the BOECs infect glioma cells. Subsequent spread from tumor cell to tumor cell leads to focal infection and cytopathic effects that decrease tumor size and, in the case of peritumoral injection, prolong survival of mice. Since MV-Edm within BOECs are not readily neutralized and because BOEC/MV-Edm search and destroy glioma cells, BOEC/MV-Edm constitute a promising novel approach for glioma therapy.

  18. Generation of Noninvasive, Quantifiable, Orthotopic Animal Models for NF2-Associated Schwannoma and Meningioma.

    PubMed

    Burns, Sarah S; Chang, Long-Sheng

    2016-01-01

    Schwannomas and meningiomas are nervous system tumors that can occur sporadically or in patients with neurofibromatosis type 2 (NF2). Mutations of the Neurofibromatosis 2 (NF2) gene are frequently observed in these tumors. Schwannomas and meningiomas cause significant morbidities, and an FDA-approved medical therapy is currently not available. The development of preclinical animal models that accurately capture the clinical characteristics of these tumors will facilitate the evaluation of novel therapeutic agents for the treatment of these tumors, ultimately leading to more productive clinical trials. Here, we describe the generation of luciferase-expressing NF2-deficient schwannoma and meningioma cells and the use of these cells to establish orthotopic tumor models in immunodeficient mice. The growth of these tumors and their response to treatment can be measured effectively by bioluminescence imaging (BLI) and confirmed by small-animal magnetic resonance imaging (MRI). These and other animal models, such as genetically-engineered models, should substantially advance the investigation of promising therapies for schwannomas and meningiomas. PMID:27259921

  19. 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

  20. Graft complications following orthotopic liver transplantation: Role of non-invasive cross-sectional imaging techniques.

    PubMed

    Boraschi, Piero; Della Pina, Maria Clotilde; Donati, Francescamaria

    2016-07-01

    Orthotopic liver transplantation is the treatment of choice in adult patients with endstage liver disease. Survival of both graft and patient has progressively improved over time due to improvements in surgical and medical treatment. However, post-transplant complications still have a significant impact on morbidity and mortality associated with transplant surgery. The most common adverse events of the graft include vascular (arterial and venous stenosis and thrombosis), biliary (leakage, strictures, stones) and parenchymal complications (hepatitis virus C infection, HCC recurrence, liver abscesses). The diagnosis of these adverse events is often challenging because of the low specificity of clinical and biologic findings. Different diagnostic algorithms have been proposed for the detection of graft complications and, in this setting, radiological evaluation plays a key role in differential diagnosis of graft complications and the exclusion of other adverse events. Ultrasound examination is established the first-line method of identifying adverse events in liver transplant recipients but a normal or a technically unsatisfactory study cannot exclude the presence of biliary, vascular and/or parenchymal complications. In these circumstances, before planning any treatment, multi-detector CT and/or MR imaging and MR cholangiography should be performed for the evaluation of vascular structures, biliary system, liver parenchyma and fluid collections. The aim of this review is to illustrate the role and state-of-the-art of non-invasive cross-sectional imaging techniques in the diagnosis and management of complications which primarily affect the graft in patients after liver transplantation. PMID:27235874

  1. An improved syngeneic orthotopic murine model of human breast cancer progression.

    PubMed

    Rashid, Omar M; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-10-01

    Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous (OP) injection in the area of the nipple, or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. ODV produced less variable-sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development . PMID:25200444

  2. 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. PMID:20180930

  3. Role of Interventional Radiology in the Treatment of Biliary Strictures Following Orthotopic Liver Transplantation

    SciTech Connect

    Righi, Dorico; Cesarani, Federico; Muraro, Emanuele; Gazzera, Carlo; Salizzoni, Mauro; Gandini, Giovanni

    2002-01-15

    Purpose: To evaluate the efficacy and safety of percutaneous treatment of biliary strictures complicating orthotopic liver transplantation (OLT). Methods: Between October 1990 and May 2000, 619 patients underwent 678 liver transplants. Seventy of the 619 (11%) patients were found to be affected by biliary strictures by July 2000. Bilioplasty was performed in 51 of these 70 (73%) patients. A cohort of 33 of 51 (65%) patients were clinically followed for more than 12 months after the last percutaneous treatment and included in the survey results. Results: After one to three treatments 24 of 33 (73%)patients were stricture-free on ultrasound and MR cholangiography follow-up. A delayed stricture recurrence required a fourth percutaneous bilioplasty in two of 33 (6%) patients. A surgical bilioenteric anastomosis was performed in six of 33 (18%) patients.Retransplantation was performed due to ischemic damage in one of 33(3%) patients. Conclusion: Interventional radiology is an effective therapeutic alternative for the treatment of most biliary strictures complicating OLT. It has a high success rate and should be considered before surgical interventions. Elective surgery may be necessary in a few failed cases or those with more severe and extensive biliary strictures.

  4. MicroRNA-184-Mediated Inhibition of Tumour Growth in an Orthotopic Murine Model of Neuroblastoma

    PubMed Central

    TIVNAN, AMANDA; FOLEY, NIAMH H.; TRACEY, LORRAINE; DAVIDOFF, ANDREW M.; STALLINGS, RAYMOND L.

    2016-01-01

    Background Neuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system. Previous studies have shown that miR-184 expression has anti-proliferative effects in neuroblastoma cells grown in culture. Therefore, it was of interest to evaluate this effect in vivo. Materials and Methods Neuroblastoma cells overexpressing miR-184 were injected retroperitoneally into CB17-SCID mice and tumour burden was assessed by measuring bioluminescence. Overall survival was also evaluated. Results Ectopic overexpression of miR-184 in neuroblastoma cell lines is anti-proliferative. In addition, overexpression of miR-184 led to a significant reduction in tumour growth relative to negative control-treated cohorts in a xenograft model of neuroblastoma. Conclusion This study demonstrated for the first time that miR-184 significantly reduces tumour growth and increases overall survival in an orthotopic murine model of neuroblastoma through assessment of tumour growth and moribundity relative to control miRNA-treated cohorts. PMID:21115884

  5. Orthotopic Osteogenecity Enhanced by a Porous Gelatin Sponge in a Critical-Sized Rat Calvaria Defect.

    PubMed

    Kanda, Naofumi; Anada, Takahisa; Handa, Takuto; Kobayashi, Kazuhito; Ezoe, Yushi; Takahashi, Tetsu; Suzuki, Osamu

    2015-12-01

    The gelatin (Gel) powders, derived from acidic and basic extractions of porcine dermis (referred to as AE and BE), were processed for the porous sponge preparation. The disks, which were less than or greater than 500 μm in diameter [small (S) and large (L) pores, respectively] in both extractions and had an interconnected structure respectively, were implanted in critical-sized defects (CSD) of rat calvaria for 4 and 8 weeks to analyze the bone repair capability. Only the AE-S disk induced bone formation (over 60%) histomorphometrically in the CSD after 8 weeks, although the collagen orientation of the regenerated bone was still immature. Osteoblastic cell culture until 14 days did not substantiate marked superiority of AE-S disk regarding the proliferation and the differentiation, although the initial attachment was enhanced on AE-S disk than BE-L disk. The results provide the findings that a Gel sponge with a specific porous structure is capable of inducing orthotopic bone formation in vivo environment.

  6. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

    PubMed Central

    Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya-Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

    2010-01-01

    To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. PMID:20921380

  7. Effectively Screening for Coronary Artery Disease in Patients Undergoing Orthotopic Liver Transplant Evaluation.

    PubMed

    Lee, Bryan C; Li, Feng; Hanje, Adam J; Mumtaz, Khalid; Boudoulas, Konstantinos D; Lilly, Scott M

    2016-01-01

    Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated with poor outcomes when undergoing orthotopic liver transplantation (OLT); however, noninvasive screening for CAD in this population is less sensitive. In an attempt to identify redundancy, we reviewed our experience among patients undergoing CAD screening as part of their OLT evaluation between May 2009 and February 2014. Demographic, clinical, and procedural characteristics were analyzed. Of the total number of screened patients (n = 132), initial screening was more common via stress testing (n = 100; 75.8%) than coronary angiography (n = 32; 24.2%). Most with initial stress testing underwent angiography (n = 52; 39.4%). Among those undergoing angiography, CAD was common (n = 31; 23.5%). Across the entire cohort the number of traditional risk factors was linearly associated with CAD, and those with two or more risk factors were found to have CAD by angiography 50% of the time (OR 1.92; CI 1.07-3.44, p = 0.026). Our data supports that CAD is prevalent among pre-OLT patients, especially among those with 2 or more risk factors. Moreover, we identified a lack of uniformity in practice and the need for evidence-based and standardized screening protocols. PMID:27418975

  8. Preoperative risk factor analysis in orthotopic liver transplant-ation with pretransplant artificial liver support therapy

    PubMed Central

    Yuan, Jin-Zhong; Ye, Qi-Fa; Zhao, Ling-Ling; Ming, Ying-Zi; Sun, Hong; Zhu, Shai-Hong; Huang, Zu-Fa; Wang, Min-Min

    2006-01-01

    AIM: To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT). METHODS: Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d) after OLT. RESULTS: In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30d observation was: 28 kept alive and 6 patients died. CONCLUSION: Pre-operative SOFA, level of creatinine, INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly. PMID:16937506

  9. Mechanisms of hypertension during and after orthotopic liver transplantation in children

    PubMed Central

    Lawless, Stephen; Ellis, Demetrius; Thompson, Ann; Cook, D. Ryan; Esquivel, Carlos; Starzl, Thomas

    2010-01-01

    The aim of this study was to assess the hormonal alterations that may mediate the systemic hypertension that develops in patients during the perioperative period of orthotopic liver transplantation. We studied nine pediatric patients without previous hypertension or renal disease during six time points, starting before transplantation and ending at 48 hours after surgery. Hypertension developed in all patients in association with central venous pressures <10 mm Hg. Free water clearance was negative in all nine patients. Vasopressin levels increased intraoperatively but fell as hypertension developed. Atrial natriuretic factor levels increased as systemic blood pressure rose. A high level of plasma renin activity was observed in four patients with renal insufficiency. In six patients, postoperative 24-hour urinary norepinephrine excretion was within the normal age-adjusted range. These findings suggest that the combination of cyclosporine, corticosteroids, and, in some patients, an elevated plasma renin activity prevents the kidney from responding to the acute volume and salt overload with an appropriate diuresis and natriuresis, thus leading to systemic hypertension. The treatment of hypertension after liver transplantation may include salt restriction, diuretics, and, in those patients with a low creatinine excretion index, angiotensin coverting enzyme inhibitors. PMID:2527974

  10. Uptake of verteporfin by orthotopic xenograft pancreas models with different levels of aggression

    NASA Astrophysics Data System (ADS)

    O'Hara, Julia; Samkoe, Kimberley S.; Chen, Alina; Hoopes, P. Jack; Rizvi, Imran; Hasan, Tayyaba; Pogue, Brian W.

    2009-06-01

    Pancreatic cancer is an aggressive disease with a poor prognosis, usually treated with chemoradiation therapy. Interstitial photodynamic therapy is a potentially effective adjuvant treatment that is under development. In the current study, two orthotopic pancreatic cancer models (AsPC-1 and Panc-1), have been characterized with respect to growth rates, morphology and liposomal drug (Verteporfin) uptake and distribution in SCID mice. Fluorescence of Verteporfin was measured in liver and tumor in vivo using a PDT fluorescence dosimeter with measurements taken before and up to one hour after tail vein injection. Fluorescence reached a plateau by about 15 minutes and did not decrease over the first hour. At time points from 15 minutes to 24 hrs, the internal organs (kidney, spleen, pancreas, tumor, muscle, lung, liver, and skin were excised and scanned on a Typhoon imager. The ratio of fluorescence in tumor versus normal tissues was analyzed with image processing, calculated at each time point and compared to in vivo results. Tissue distribution of Verteporfin in relation to functional vasculature marked by DiOc7 was carried out on frozen sections. Final analysis will result in determination of the ideal time point to administer light to achieve maximum tumor destruction while preserving normal tissue.

  11. Prolonged Delirium With Catatonia Following Orthotopic Liver Transplant Responsive to Memantine.

    PubMed

    Brown, Gregory D; Muzyk, Andrew J; Preud'homme, Xavier A

    2016-03-01

    A 59-year-old man with nonalcoholic steatohepatitis cirrhosis underwent an orthotopic liver transplant and experienced a complicated postoperative course, including a prolonged delirium. After discharge to rehabilitation, he had 2 subsequent admissions for delirium. On the first readmission, the transplant team started the patient on risperidone and resumed treatment with sertraline. On his second readmission, neurology and psychiatry were consulted. On evaluation, the patient demonstrated signs of catatonia. On the basis of recommendations from psychiatry, the risperidone and sertraline were stopped, and the patient was started on mirtazapine. He failed to demonstrate improvement within the next 48 hours. Extensive work-up demonstrated a multifactorial etiology for his delirium, including calcineurin-related neuropsychiatric toxicity from tacrolimus leading to possible posterior reversible encephalopathy syndrome. However, after the initiation of memantine on hospital day 3-before the cessation of tacrolimus-the patient demonstrated marked improvement in mental status and motor symptoms. His magnetic resonance imaging, in addition to findings that raised concerns about posterior reversible encephalopathy syndrome, had demonstrated bilateral basal ganglia abnormalities on T1 imaging of uncertain origin. It is postulated that these findings served as predisposing factors for the patient's catatonic symptoms. Although it has been described in case reports following liver transplant, catatonia remains an underrecognized neuropsychiatric complication following liver transplant. This case demonstrates the effectiveness of memantine, an N-methyl-D-aspartic acid antagonist that decreases glutamine excitotoxicity, as a potential treatment for catatonia in postliver transplant patients. PMID:27138082

  12. Establishment of an Orthotopic Xenograft Mice Model of Retinoblastoma Suitable for Preclinical Testing.

    PubMed

    Cassoux, Nathalie; Thuleau, Aurélie; Assayag, Franck; Aerts, Isabelle; Decaudin, Didier

    2015-04-01

    Retinoblastoma is a rare cancer that occurs during childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy, which is known to increase the risk of secondary cancers in genetically predisposed patients. Multimodality therapy (usually intravenous but also intra-arterial and intravitreal chemotherapy, transpupillary thermotherapy, cryotherapy, or brachytherapy) has recently improved the eye salvage rate in retinoblastoma and has led to a decreased need for external beam radiotherapy. However, the treatment of advanced intraocular retinoblastoma remains a real challenge, especially in cases of vitreous and subretinal seeding. There is a need for alternative and less toxic therapies as well as for better ways to administer the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper describes the different xenograft rodent models published in the literature so far. We will also describe a new orthotopic xenografted retinoblastoma model in immunodeficient mice, which is suitable for preclinical assays. The xenograft model was established from tumor tissue obtained directly from surgical samples and closely mimics human retinoblastoma.

  13. Transcatheter Splenic Artery Occlusion for Treatment of Splenic Artery Steal Syndrome After Orthotopic Liver Transplantation

    SciTech Connect

    Uflacker, Renan; Selby, J. Bayne; Chavin, Kenneth; Rogers, Jeffrey; Baliga, Prabhakar

    2002-08-15

    Purpose: To review some aspects of the problem of splenic artery steal syndrome as cause of ischemia in transplanted livers and treatment by selective splenic artery occlusion. Materials and Methods: Eleven liver transplant patients from a group of 350 patients, nine men and two women,ranging in age from 40 years to 61 years (mean 52 years), presented with biochemical evidences of liver ischemia and failure, ranging from one to 60 days following orthotopic liver transplantation. Diagnosis of splenic artery steal syndrome was suspected by elevated enzymes, Doppler ultrasound and confirmed by celiac angiogram. Patients with confirmed hepatic artery thrombosis before angiography were excluded from the study. Embolization with Gianturco coils was performed. Results: All patients were treated by splenic artery embolization with Gianturco coils. The 11 patients improved clinically within 24 hours of the procedure with significant change in the biochemical and clinical parameters. Followup ranged from one month to two years. One of the 11 patient initially improved, but developed hepatic artery thrombosis within 24 hours of the embolic treatment,requiring surgical repair. Conclusion: Splenicartery steal syndrome following liver transplantation surgery can be diagnosed by celiac angiography, and effectively treated by splenic artery embolization with coils. Embolization is one of the treatments available, it is minimally invasive, and leads to immediate clinical improvement. Hepatic artery thrombosis is a possible complication of the procedure.

  14. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts1

    PubMed Central

    Herrmann, Kelsey; Erokwu, Bernadette O.; Johansen, Mette L.; Basilion, James P.; Gulani, Vikas; Griswold, Mark A.; Flask, Chris A.; Brady-Kalnay, Susann M.

    2016-01-01

    Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI) techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents. PMID:27084431

  15. Hepatic artery thrombosis after orthotopic liver transplantation: 3 patients with collateral formation and conservative treatment.

    PubMed

    Fouzas, I; Sklavos, A; Bismpa, K; Paxiadakis, I; Antoniadis, N; Giakoustidis, D; Katsiki, E; Tatsou, N; Mouloudi, E; Karapanagiotou, A; Tsitlakidis, A; Karakatsanis, A; Patsiaoura, K; Petridis, A; Gakis, D; Imvrios, G; Papanikolaou, V

    2012-11-01

    Hepatic artery thrombosis (HAT), a serious complication after orthotopic liver transplantation (OLT), can lead to patient death in the absence of revascularization or retransplantation. Herein we have presented clinical characteristics, imaging findings, and long-term outcomes of 3 OLT patients with HAT who were treated conservatively and developed hepatic arterial collaterals. These patients underwent transplantation due to hepatitis B cirrhosis, cryptogenic cirrhosis, or hepatitis C infection and alcoholic disease. They presented with bile duct stenosis and/or a bile leak at 1, 3, and 36 months after transplantation, respectively, and were treated with percutaneous drainage and stent placement, endoscopic retrograde cholangio-pancreatography (ERCP), or reanastomosis of the bile duct over a T tube. HAT was confirmed using multidetector computed tomography (MDCT) 3-dimensional (3D) angiography and Doppler sonography. They survive in good condition with normal liver function at 30, 50, and 42 months after OLT, respectively. Development of collateral arterial circulation to the liver graft was detected with MDCT 3D angiography and Doppler sonography. From our experience with 3 patients and a literature review, we believe that there are a number of patients who experience long-term survival after the diagnosis of irreversible HAT and the development of collaterals. Although this group is at high risk for sepsis and biliary complications, these are usually self-limiting complications due to improved treatment regimens. The development of collateral arterial flow may also be beneficial.

  16. Establishment of an Orthotopic Xenograft Mice Model of Retinoblastoma Suitable for Preclinical Testing.

    PubMed

    Cassoux, Nathalie; Thuleau, Aurélie; Assayag, Franck; Aerts, Isabelle; Decaudin, Didier

    2015-04-01

    Retinoblastoma is a rare cancer that occurs during childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy, which is known to increase the risk of secondary cancers in genetically predisposed patients. Multimodality therapy (usually intravenous but also intra-arterial and intravitreal chemotherapy, transpupillary thermotherapy, cryotherapy, or brachytherapy) has recently improved the eye salvage rate in retinoblastoma and has led to a decreased need for external beam radiotherapy. However, the treatment of advanced intraocular retinoblastoma remains a real challenge, especially in cases of vitreous and subretinal seeding. There is a need for alternative and less toxic therapies as well as for better ways to administer the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper describes the different xenograft rodent models published in the literature so far. We will also describe a new orthotopic xenografted retinoblastoma model in immunodeficient mice, which is suitable for preclinical assays. The xenograft model was established from tumor tissue obtained directly from surgical samples and closely mimics human retinoblastoma. PMID:27171982

  17. A novel mucosal orthotopic murine model of human papillomavirus-associated genital cancers.

    PubMed

    Decrausaz, Loane; Gonçalves, Ana-Rita; Domingos-Pereira, Sonia; Pythoud, Christelle; Stehle, Jean-Christophe; Schiller, John; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2011-05-01

    Cervical cancer results from infection with high-risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV-expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine-induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV-associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7-expressing tumor cells transduced with a luciferase-encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80-90% after nonoxynol-9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions. This novel genital HPV-tumor model by requiring GM homing of vaccine-induced immune responses able to overcome local immuno-suppression may be more representative of the situation occurring in patients upon therapeutic vaccination. PMID:20635385

  18. An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis

    PubMed Central

    Reiberger, Thomas; Chen, Yunching; Ramjiawan, Rakesh R; Hato, Tai; Fan, Christopher; Samuel, Rekha; Roberge, Sylvie; Huang, Peigen; Lauwers, Gregory Y; Zhu, Andrew X; Bardeesy, Nabeel; Jain, Rakesh K; Duda, Dan G

    2016-01-01

    Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4−/−Stk3F/− (also known as Mst1−/−Mst2F/−; F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis. PMID:26203823

  19. Technique of Porcine Liver Procurement and Orthotopic Transplantation using an Active Porto-Caval Shunt

    PubMed Central

    Spetzler, Vinzent N.; Goldaracena, Nicolas; Knaak, Jan M.; Louis, Kristine S.; Selzner, Nazia; Selzner, Markus

    2015-01-01

    The success of liver transplantation has resulted in a dramatic organ shortage. Each year, a considerable number of patients on the liver transplantation waiting list die without receiving an organ transplant or are delisted due to disease progression. Even after a successful transplantation, rejection and side effects of immunosuppression remain major concerns for graft survival and patient morbidity. Experimental animal research has been essential to the success of liver transplantation and still plays a pivotal role in the development of clinical transplantation practice. In particular, the porcine orthotopic liver transplantation model (OLTx) is optimal for clinically oriented research for its close resemblance to human size, anatomy, and physiology. Decompression of intestinal congestion during the anhepatic phase of porcine OLTx is important to guarantee reliable animal survival. The use of an active porto-caval-jugular shunt achieves excellent intestinal decompression. The system can be used for short-term as well as long-term survival experiments. The following protocol contains all technical information for a stable and reproducible liver transplantation model in pigs including post-operative animal care. PMID:25992583

  20. A novel mucosal orthotopic murine model of human papillomavirus-associated genital cancers.

    PubMed

    Decrausaz, Loane; Gonçalves, Ana-Rita; Domingos-Pereira, Sonia; Pythoud, Christelle; Stehle, Jean-Christophe; Schiller, John; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2011-05-01

    Cervical cancer results from infection with high-risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV-expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine-induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV-associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7-expressing tumor cells transduced with a luciferase-encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80-90% after nonoxynol-9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions. This novel genital HPV-tumor model by requiring GM homing of vaccine-induced immune responses able to overcome local immuno-suppression may be more representative of the situation occurring in patients upon therapeutic vaccination.

  1. Establishment of an Orthotopic Xenograft Mice Model of Retinoblastoma Suitable for Preclinical Testing

    PubMed Central

    Cassoux, Nathalie; Thuleau, Aurélie; Assayag, Franck; Aerts, Isabelle; Decaudin, Didier

    2015-01-01

    Retinoblastoma is a rare cancer that occurs during childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy, which is known to increase the risk of secondary cancers in genetically predisposed patients. Multimodality therapy (usually intravenous but also intra-arterial and intravitreal chemotherapy, transpupillary thermotherapy, cryotherapy, or brachytherapy) has recently improved the eye salvage rate in retinoblastoma and has led to a decreased need for external beam radiotherapy. However, the treatment of advanced intraocular retinoblastoma remains a real challenge, especially in cases of vitreous and subretinal seeding. There is a need for alternative and less toxic therapies as well as for better ways to administer the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper describes the different xenograft rodent models published in the literature so far. We will also describe a new orthotopic xenografted retinoblastoma model in immunodeficient mice, which is suitable for preclinical assays. The xenograft model was established from tumor tissue obtained directly from surgical samples and closely mimics human retinoblastoma. PMID:27171982

  2. Real Time Metastatic Route Tracking of Orthotopic PC-3-GFP Human Prostate Cancer Using Intravital Imaging.

    PubMed

    Zhang, Yong; Wang, Xiaoen; Hoffman, Robert M; Seki, Naohiko

    2016-04-01

    The cellular basis of metastasis is poorly understood. An important step to understanding this process is to be able to visualize the routes by which cancer cells migrate from the primary tumor to various distant sites to eventually form metastasis. Our laboratory previously developed single-cell in vivo imaging using fluorescent proteins to label cancer cells. In the present study, using PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) and orthotopic tumor transplantation, we have imaged in live mice various highly diverse routes by which PC-3 cells metastasize superiorly and inferiorly to distant sites, including in the portal area, stomach area, and urogenital system. Imaging began at day 9, at which time distant metastasis had already occurred, and increased at each imaging point at days 10, 13, 14, and 16. Metastatic cells were observed migrating superiorly and inferiorly from the primary tumor as well as in lymphatic channels and trafficking in various organ systems demonstrating that PC-3 has multiple metastatic routes similar to hormone-independent advanced-stage prostate cancer in the clinic. PMID:26515240

  3. TCGA data and patient-derived orthotopic xenografts highlight pancreatic cancer-associated angiogenesis

    PubMed Central

    Gore, Jesse; Craven, Kelly E.; Wilson, Julie L.; Cote, Gregory A.; Cheng, Monica; Nguyen, Hai V.; Cramer, Harvey M.; Sherman, Stuart; Korc, Murray

    2015-01-01

    Pancreatic ductal adenocarcinomas (PDACs) overexpress pro-angiogenic factors but are not viewed as vascular. Using data from The Cancer Genome Atlas we demonstrate that a subset of PDACs exhibits a strong pro-angiogenic signature that includes 37 genes, such as HDAC9, that are overexpressed in PDAC arising in KRC mice, which express mutated Kras and lack RB. Moreover, patient-derived orthotopic xenografts can exhibit tumor angiogenesis, whereas conditioned media (CM) from KRC-derived pancreatic cancer cells (PCCs) enhance endothelial cell (EC) growth and migration, and activate canonical TGF-β signaling and STAT3. Inhibition of the type I TGF-β receptor with SB505124 does not alter endothelial activation in vitro, but decreases pro-angiogenic gene expression and suppresses angiogenesis in vivo. Conversely, STAT3 silencing or JAK1–2 inhibition with ruxolitinib blocks CM-enhanced EC proliferation. STAT3 disruption also suppresses endothelial HDAC9 and blocks CM-induced HDAC9 expression, whereas HDAC9 re-expression restores CM-enhanced endothelial proliferation. Moreover, ruxolitinib blocks mitogenic EC/PCC cross-talk, and suppresses endothelial p-STAT3 and HDAC9, and PDAC progression and angiogenesis in vivo, while markedly prolonging survival of KRC mice. Thus, targeting JAK1–2 with ruxolitinib blocks a final pathway that is common to multiple pro-angiogenic factors, suppresses EC-mediated PCC proliferation, and may be useful in PDACs with a strong pro-angiogenic signature. PMID:25762644

  4. Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and angiogenesis in an orthotopic glioma model.

    PubMed

    Zhang, Yu-Hui; Yue, Zhi-Jian; Zhang, He; Tang, Gu-Sheng; Wang, Yang; Liu, Jian-Min

    2010-11-01

    Temozolomide (TM) has anti-tumor activity in patients with malignant glioma. Implantable poly (D,L-lactide-co-glycolide) (PLGA) microparticles of TM (TM-MS) have been developed, enhancing the cytotoxicity of TM to Glioma C6 cells. Vatalanib, as anti-angiogenic agent, has also shown anti-tumor activity with malignant gliomas. We examined the combined effects of TM-MS and vatalanib in a rat orthotopic glioma model and found TM-MS offered a greater tumor inhibition than TM, and combination treatment with both of them improved the survival time versus single agent therapy. The combination treatment also demonstrated an inhibition to rat glioma tumors, a significant decrease in cell proliferation, an increase in apoptosis, and a lower microvessel density within the glioma tumors. The results suggest that TM-MS can more effectively inhibit tumor than TM, and combination treatment with TM-MS and vatalanib inhibits tumor growth and angiogenesis and may prove to be a promising therapy for malignant gliomas. PMID:20816959

  5. Dexmedetomidine Pretreatment Attenuates Kidney Injury and Oxidative Stress during Orthotopic Autologous Liver Transplantation in Rats

    PubMed Central

    Wu, Shan; Jin, Yi; Wang, Yiheng; Cai, Jun

    2016-01-01

    This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecific α2 receptor blocker) + high dose Dex (group B1), ARC239 (a specific α2B/c receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specific α2A receptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (all P < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 through α2A receptor, increases the antioxidant levels, and attenuates renal injury during OALT. PMID:26682005

  6. Hyaluronidase gene profiling and role of hyal-1 overexpression in an orthotopic model of prostate cancer.

    PubMed

    Patel, Sonal; Turner, Paul R; Stubberfield, Colin; Barry, Eleanor; Rohlff, Christian R; Stamps, Alasdair; McKenzie, Edward; Young, Kathryn; Tyson, Kerry; Terrett, Jon; Box, Gary; Eccles, Suzanne; Page, Martin J

    2002-02-01

    The mRNA levels of hyal-1, hyal-2, LUCA3 and PH20, the 4 hyaluronidases with demonstrated endoglucosaminidase activity, were extensively profiled in normal and tumor tissues and cell lines, using dot blot analysis and quantitative PCR. In normal tissues, hyal-1, hyal-2 and LUCA3 all showed unique patterns of mRNA expression, but were generally of widespread distribution, whereas PH20 mRNA was restricted to testes. In a small set of breast tumor samples, no elevations in hyal-1, hyal-2 or LUCA3 mRNA were seen. Hyaluronidase activity measured by a novel assay or zymography was also not elevated in sera from a number of breast cancer patients, compared to sera from normal volunteers. In ex vivo xenograft tumor cell lines, however, hyal-1 or hyal-2 mRNA levels were frequently elevated, whereas LUCA3 was only infrequently elevated and PH20 not at all. Two cell lines were engineered to overexpress hyal-1: a breast cancer line (CAL51) and a prostate cancer line (PC3M). Although the in vitro properties of the hyal-1 overexpressing cell lines were indistinguishable from the parental cells, the orthotopic growth of hyal-1 expressing PC3M cells in nu/nu mice resulted in significantly increased numbers of metastases, supportive of a role for hyal-1 in extravasation and metastatic tumor formation in this model of prostate cancer. PMID:11802201

  7. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    SciTech Connect

    Pennock, J.L.; Reitz, B.A.; Beiber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either Cy A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  8. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    SciTech Connect

    Pennock, J.L.; Reitz, B.A.; Bieber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either CY A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI plus Cy A when compared with using Cy A alone. TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  9. Aerocoat 7 Replacement Coatings

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Kennedy Space Center has used Aerocoat 7 (AR-7) to protect stainless-steel flex hoses at Launch Complex (LC-39) and hydraulic lines of the Mobile Launcher Platform (MLP) because it provides excellent corrosion protection in low-temperature applications. The Sovereign Company produced AR-7 exclusively for NASA but discontinued production because the coating released high levels of volatile organic compounds (VOCs) and had a significant environmental impact. The purpose of this project was to select and evaluate potential replacement coatings for AR-7 that would be more environmentally sound. The physical and mechanical properties of commercially available coatings were investigated through the Internet. The ideal coating would be fluid enough to penetrate the outer mesh of a stainless-steel flex hose and coat the inner hose, and flexible enough to withstand the movement of the hose, as well as the expansion and contraction of its metal caused by changes in temperature.

  10. Antenna grout replacement system

    NASA Technical Reports Server (NTRS)

    Mcclung, C. E. (Inventor)

    1983-01-01

    An epoxy grout suitable for use in mounting and positioning bearing runner plates used in hydrostatic bearing assemblies for rotatably mounting large radio telescope structures to stationary support pedestals is described. The epoxy grout may be used in original mountings or may be used as part of a replacement system for repairing cavities in existing grout resulting from grout deterioration. The epoxy grout has a relatively short work life and cure time even in the presence of hydraulic oil. The epoxy grout cures without shrinking or sagging to form a grout which is sufficiently strong and durable to provide a grout especially well suited for use under the high pressure loading and close tolerance requirements of large hydrostatic bearing assemblies.

  11. Variations of intestinal motor activity in bladder replacements and in the intestine.

    PubMed

    Lobel, B; Guille, F; Olivo, J F; Gosselin, A; Goldwasser, B

    1993-12-01

    Urinary reservoirs are made from intestinal segments. The motor activity of the intestinal tract is regulated by hormonal and neurological controls. This study compares the motor activity of intestine in situ with those of a neobladder, following oral intake. The changes in motor activity before and after ingestion of standardized 570 Kcal meal were measured simultaneously in the duodenum and in the neobladder of 4 patients who underwent a Camey tubularized ileocystoplasty. Similar motor movements were produced in the graft and in the duodenum. Modifications due to oral intake were then measured in 14 patients with various types of urinary reservoirs (ilea, ileo-colic or colic; and tubularized or detubularized) by measuring the pressure inside the graft. After oral intake the compliance of the detubularized colic and ileocolic reservoirs was greater than that of ileal reservoirs, even after detubularization, since the motor activity and the basal pressure increased greatly in the tubularized or detubularized ileal bladders and much less in the detubularized colic and ileocolic bladders. It is well known that digestion is maximal in the second half of the night, therefore this link between intestinal and neobladder motor activity might explain one of several mechanisms involved in nocturnal increase in reservoir pressure and urine incontinence.

  12. Splenic Artery Syndrome After Orthotopic Liver Transplantation: Treatment With the Amplatzer Vascular Plug

    SciTech Connect

    Maurer, M. H.; Mogl, M. T.; Podrabsky, P.; Denecke, T.; Grieser, C.; Froeling, V.; Scheurig-Muenkler, C.; Guckelberger, O.; Kroencke, T. J.

    2011-12-15

    Purpose: To evaluate the safety and efficacy of the Amplatzer vascular plug (AVP) for embolization of the splenic artery in patients with hepatic hypoperfusion after orthotopic liver transplantation (OLT). Materials and Methods: Thirteen patients (9 men and 4 women) with a mean age of 56 years (range 22-70) who developed splenic artery syndrome after OLT with decreased liver perfusion and clinically relevant impairment of liver function (increased transaminase or serum bilirubin levels, thrombocytopenia, and/or therapy-refractory ascites) were treated by embolization of the proximal third of the splenic artery using the AVP. The plugs ranged in diameter from 6 to 16 mm, and they were introduced through femoral (n = 9), axillary (n = 3), or brachial (n = 1) access using a 5F or 8F guiding catheter. Results: The plugs were successfully placed, and complete occlusion of the splenic artery was achieved in all patients. Placement of two plugs was necessary for complete occlusion in 3 of the 13 patients. Occlusion took on average 10 min (range 4-35). There was no nontarget embolization or plug migration into more distal segments of the splenic artery. All patients showed improved arterial perfusion, including the liver periphery, on postinterventional angiogram. After embolization, liver function parameters (transaminase and bilirubin levels) improved with normalization of concomitant thrombocytopenia and a decrease in ascites volume. Conclusion: Our initial experience in a small patient population with SAS suggests that the AVP enables precise embolization of the proximal splenic artery, thus providing safe and effective treatment for poor liver perfusion after OLT due to SAS.

  13. Post-reperfusion Syndrome and Outcome Variables after Orthotopic Liver Transplantation

    PubMed Central

    Khosravi, M. B.; Sattari, H.; Ghaffaripour, S.; Lahssaee, M.; Salahi, H.; Sahmeddini, M. A.; Bahador, A.; Nikeghbalian, S.; Parsa, S.; Shokrizadeh, S.; Malek-Hosseini, S. A.

    2010-01-01

    Background: Post-reperfusion syndrome (PRS) is an important complication during liver transplantation. Objective: We studied the occurrence and severity of PRS in patients who underwent orthotopic liver transplantation (OLT) to investigate how PRS was correlated to clinical variables and outcomes. Methods: We retrospectively recorded intra- and peri-operative data for 184 adult patients who received cadaveric OLT during a 3-year period from 2005 to 2008. Patients were divided into two groups according to the severity of PRS: Group 1 (mild or no PRS) comprised 152 patients; and group 2 (significant PRS) consisted of 32 patients. Results: There were no significant differences in demographic and pre-operative data between groups. Group 2 had more total blood loss than group 1 (p=0.036), especially after reperfusion (p=0.023). Group 2 required more packed red cell transfusions (p=0.005), more fresh frozen plasma (p=0.003) and more platelets (p=0.043) than group 1. Fibrinolysis was more frequent in group 2 (p=0.004). Hospital stay in group 2 was significantly longer than in group 1 (p=0.034), but the frequencies of other outcomes including infection, retransplantation, dialysis, rejection and extended donor criteria did not differ significantly between groups. Conclusions: Bleeding, blood transfusion and fibrinolysis occurred more often in the group of severe PRS after reperfusion. Although postoperative complications like rejection, infection and the dialysis rate were not significantly different in the two groups, hospital stay was more prolonged in the group with severe PRS. PMID:25013576

  14. 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.

  15. Evaluation of pleth variability index as a predictor of fluid responsiveness during orthotopic liver transplantation.

    PubMed

    Konur, Huseyin; Erdogan Kayhan, Gulay; Toprak, Huseyin Ilksen; Bucak, Nizamettin; Aydogan, Mustafa Said; Yologlu, Saim; Durmus, Mahmut; Yılmaz, Sezai

    2016-07-01

    Fluid management is challenging and still remains controversial in orthotopic liver transplantation (OLT). The pleth variability index (PVI) has been shown to be a reliable predictor of fluid responsiveness of perioperative and critically ill patients; however, it has not been evaluated in OLT. This study was designed to examine whether the PVI can reliably predict fluid responsiveness in OLT and to compare PVI with other hemodynamic indexes that are measured using the PiCCO2 monitoring system. Twenty-five patients were enrolled in this study. Each patient was monitored using the noninvasive Masimo and PiCCO2 monitoring system. PVI was obtained with a Masimo pulse oximeter. Cardiac index was obtained using a transpulmonary thermodilution technique (CITPTD). Stroke volume variation (SVV), pulse pressure variation, and systemic vascular resistance index were measured using the PiCCO2 system. Fluid loading (10 mL/kg colloid) was performed at two different phases during the operation, and fluid responsiveness was defined as an increase in CITPTD ≥ 15%. During the dissection phase and the anhepatic phase, respectively, 14 patients (56%) and 18 patients (75%) were classified as responders. There were no differences between the baseline values of the PVI of responders and nonresponders. Area under the curve for PVI was 0.56 (sensitivity 35%, specificity 90%, p = 0.58) at dissection phase, and was 0.55 (sensitivity 55%, specificity 66%, p = 0.58) at anhepatic phase. Of the parameters, a higher area under the curve value was found for SVV. We conclude that PVI was unable to predict fluid responsiveness with sufficient accuracy in patients undergoing OLT, but the SVV parameter was reliable. PMID:27450027

  16. Dynamics of the spleen and its significance in a murine H22 orthotopic hepatoma model

    PubMed Central

    Li, Baohua; Zhang, Shu; Huang, Na; Chen, Haiyan; Wang, Peijun; Li, Jun; Pu, Yansong; Yang, Jun

    2016-01-01

    The dynamics of the spleen during tumor progression remains incompletely understood. In this study, we established a murine H22 orthotopic hepatoma model and dynamically detected alterations in the percentages of immunocytes in the spleen. We observed a prominent myeloid-derived suppressor cell (MDSC) accumulation during the early response which persisted through all the stages of tumor growth. In addition, the percentage of regulatory T cells (Tregs) increased by week 2. Although the percentage of CD3+CD49b+ natural killer T (NKT) cells increased by day 3, and that of CD3+CD4+ T cells slightly increased by week 1, they decreased to either normal or lower levels compared with those of normal mice. The percentages of total CD3+, CD3+CD4+, and CD3+CD8+ T cells decreased by week 2, and that of NK cells decreased by week 3. The activation of non-Treg CD4+ T cells was scarce. Moreover, splenic MDSCs of tumor-bearing mice suppressed the activation of splenocytes. Therefore, a negative immune response gradually prevailed over a positive immune response during tumor growth. In addition, splenectomy was performed at the time of tumor inoculation, and we found that splenectomy could prolong the survival time, reduce the tumor weights, decrease the ascites volumes, and ameliorate the immune status of the tumor-bearing mice. Splenectomy also decreased the percentage of MDSCs and increased the percentages of CD8+ T cells, NK, and NKT cells in tumor tissues. Additionally, splenectomy decreased the percentage of MDSCs and increased that of CD8+ T cells in peripheral blood. Overall, our findings suggest that immune-negative cells are dominant in the spleen during tumor progression. Splenectomy could be helpful to improve the immune responses of tumor-bearing hosts. PMID:26989085

  17. 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.

  18. Transgenic animals in experimental xenotransplantation models: orthotopic heart transplantation in the pig-to-baboon model.

    PubMed

    Brandl, U; Michel, S; Erhardt, M; Brenner, P; Burdorf, L; Jöckle, H; Bittmann, I; Rössle, M; Mordstein, V; Baschnegger, H; Bauer, A; Hammer, C; Reichart, B; Schmoeckel, M

    2007-03-01

    Pig organs are at risk for hyperacute and acute vascular rejection mediated by anti-pig antibodies, mainly binding to the Galalpha(1,3)Gal epitope. Acute cellular rejection is characterized by progressive infiltration of mononuclear cells. There is an ongoing search for immunosuppressive regimens that provide adequate protection against all patterns of xenograft rejection, but have no severe impact on the condition of xenograft recipients. Herein orthotopic heart transplantations were performed from hDAF or hCD46 piglets to nonsplenectomized baboons. Basic immunosuppression consisted of tacrolimus, sirolimus, GAS914, steroids, and ATG. Group 1 received basic immunosuppression. Group 2 was additionally treated with rituximab and group 3 with half-dose cyclophosphamide. Group 4 received cyclophosphamide and an anti-HLA-DR antibody. Three baboons received GAS914 and TPC. Monitoring included the regular assessment of anti-porcine antibodies, blood counts, therapeutic drug monitoring, and graft histology. Two grafts failed due to technical mistakes. In group 1, baboons died after 1 and 9 days. In group 2, maximum survival was 30 hours. In group 3, baboons lived 20 hours, 25 days, and 14 days. Group 4 survival times were 9.5 hours, 5.5 hours, 4 days, 34 hours, and 3 days. An increase of non-Galalpha(1,3)Gal antibodies was observed. Depositions of immunoglobulins and complement revealed a humoral rejection process. No cellular infiltration could be observed. In conclusion, suppressing cellular rejection with half-dose cyclophosphamide together with tacrolimus and sirolimus produced longer graft survival with a good general condition. Prevention of acute xenograft rejection further needs inhibition of non-Galalpha(1,3)Gal cytotoxicity by sufficient depression of B-cell activation.

  19. 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.

  20. Endoscopic retrograde cholangiopancreatography in patients with biliary complications after orthotopic liver transplantation: outcomes and complications.

    PubMed

    Sanna, C; Saracco, G M; Reggio, D; Moro, F; Ricchiuti, A; Strignano, P; Mirabella, S; Ciccone, G; Salizzoni, M

    2009-05-01

    Biliary complications after orthotopic liver transplantation (OLT) still remain a major cause of morbidity and mortality. The most frequent complications are strictures and leakages in OLT cases with duct-to-duct biliary reconstruction (D-D), which can be treated with dilatation or stent placement during endoscopic retrograde cholangiopancreatography (ERCP), although this procedure is burdened with potentially severe complications, such as retroperitoneal perforation, acute pancreatitis, septic cholangitis, bleeding, recurrence of stones, strictures due to healing process. The aim of the study was to analyze the outcome of this treatment and the complications related to the procedure. Among 1634 adult OLTs, we compared postprocedural complications and mortality rates with a group of 5852 nontransplanted patients (n-OLTs) who underwent ERCP. Of 472 (28,8%) post-OLT biliary complications, 319 (67.6%) occurred in D-D biliary anstomosis cases and 94 (29.5%) patients underwent 150 ERCP sessions. Among 49/80 patients (61.2%) who completed the procedure, ERCP treatment was successful. Overall complication rate was 10.7% in OLT and 12.8% in n-OLT (P = NS). Compared with the n-OLT group, post-ERCP bleeding was more frequent in OLT (5.3% vs 1.3%, P = .0001), while the incidence of pancreatitis was lower (4.7% vs 9.6%, P = .04). Procedure-related mortality rate was 0% in OLT and 0.1% in n-OLT (P = NS). ERCP is a safe procedure for post-OLT biliary complications in the presence of a D-D anastomosis. Morbidity and mortality related with this procedure are acceptable and similar to those among nontransplanted population. PMID:19460551

  1. A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields.

    PubMed

    Chen, Ru; Sain, Nova M; Harlow, K Tyler; Chen, Yeong-Jer; Shires, Peter K; Heller, Richard; Beebe, Stephen J

    2014-10-01

    Strategies for treating liver cancer using radiation, chemotherapy combinations and tyrosine kinase inhibitors targeting specific mutations have provided longer survival times, yet multiple treatments are often needed and recurrences with new malignant phenotypes are not uncommon. New and innovative treatments are undoubtedly needed to successfully treat liver cancer. Over the last decade, nanosecond pulsed electric fields (nsPEFs) have shown promise in pre-clinical studies; however, these have been limited to treatment of skin cancers or xenographs in mice. In the present report, an orthotopic hepatocellular carcinoma (HCC) model is established in rats using N1-S1 HCC cells. Data demonstrate a response rate of 80-90% when 1000 pulses are delivered with 100ns durations, electric field strengths of 50kV/cm and repetition rates of 1Hz. N1-S1 tumours treated with nsPEFs expressed significant number of cells with active caspase-3 and caspase-9, but not caspase-8, indicating an intrinsic apoptosis mechanism(s) as well as caspase-independent mechanisms. Most remarkably, rats with successfully ablated tumours failed to re-grow tumours when challenged with a second injection of N1-S1 cells when implanted in the same or different liver lobe that harboured the original tumour. Given this protective effect, infiltration of immune cells and the presence of granzyme B expressing cells within days of treatment suggest the possibility of an anti-tumour adaptive immune response. In conclusion, NsPEFs not only eliminate N1-S1 HCC tumours, but also may induce an immuno-protective effect that defends animals against recurrences of the same cancer.

  2. Standardized orthotopic xenografts in zebrafish reveal glioma cell-line-specific characteristics and tumor cell heterogeneity

    PubMed Central

    Welker, Alessandra M.; Jaros, Brian D.; Puduvalli, Vinay K.; Imitola, Jaime; Kaur, Balveen; Beattie, Christine E.

    2016-01-01

    ABSTRACT Glioblastoma (GBM) is a deadly brain cancer, for which few effective drug treatments are available. Several studies have used zebrafish models to study GBM, but a standardized approach to modeling GBM in zebrafish was lacking to date, preventing comparison of data across studies. Here, we describe a new, standardized orthotopic xenotransplant model of GBM in zebrafish. Dose-response survival assays were used to define the optimal number of cells for tumor formation. Techniques to measure tumor burden and cell spread within the brain over real time were optimized using mouse neural stem cells as control transplants. Applying this standardized approach, we transplanted two patient-derived GBM cell lines, serum-grown adherent cells and neurospheres, into the midbrain region of embryonic zebrafish and analyzed transplanted larvae over time. Progressive brain tumor growth and premature larval death were observed using both cell lines; however, fewer transplanted neurosphere cells were needed for tumor growth and lethality. Tumors were heterogeneous, containing both cells expressing stem cell markers and cells expressing markers of differentiation. A small proportion of transplanted neurosphere cells expressed glial fibrillary acidic protein (GFAP) or vimentin, markers of more differentiated cells, but this number increased significantly during tumor growth, indicating that these cells undergo differentiation in vivo. By contrast, most serum-grown adherent cells expressed GFAP and vimentin at the earliest times examined post-transplant. Both cell types produced brain tumors that contained Sox2+ cells, indicative of tumor stem cells. Transplanted larvae were treated with currently used GBM therapeutics, temozolomide or bortezomib, and this resulted in a reduction in tumor volume in vivo and an increase in survival. The standardized model reported here facilitates robust and reproducible analysis of glioblastoma tumor cells in real time and provides a platform for

  3. Intraductal Delivery of Adenoviruses Targets Pancreatic Tumors in Transgenic Ela-myc Mice and Orthotopic Xenografts

    PubMed Central

    José, Anabel; Sobrevals, Luciano; Camacho-Sánchez, Juan Miguel; 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<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. PMID:23328228

  4. Antenna Controller Replacement Software

    NASA Technical Reports Server (NTRS)

    Chao, Roger Y.; Morgan, Scott C.; Strain, Martha M.; Rockwell, Stephen T.; Shimizu, Kenneth J.; Tehrani, Barzia J.; Kwok, Jaclyn H.; Tuazon-Wong, Michelle; Valtier, Henry; Nalbandi, Reza; Wert, Michael; Leung, Patrick

    2010-01-01

    The Antenna Controller Replacement (ACR) software accurately points and monitors the Deep Space Network (DSN) 70-m and 34-m high-efficiency (HEF) ground-based antennas that are used to track primarily spacecraft and, periodically, celestial targets. To track a spacecraft, or other targets, the antenna must be accurately pointed at the spacecraft, which can be very far away with very weak signals. ACR s conical scanning capability collects the signal in a circular pattern around the target, calculates the location of the strongest signal, and adjusts the antenna pointing to point directly at the spacecraft. A real-time, closed-loop servo control algorithm performed every 0.02 second allows accurate positioning of the antenna in order to track these distant spacecraft. Additionally, this advanced servo control algorithm provides better antenna pointing performance in windy conditions. The ACR software provides high-level commands that provide a very easy user interface for the DSN operator. The operator only needs to enter two commands to start the antenna and subreflector, and Master Equatorial tracking. The most accurate antenna pointing is accomplished by aligning the antenna to the Master Equatorial, which because of its small size and sheltered location, has the most stable pointing. The antenna has hundreds of digital and analog monitor points. The ACR software provides compact displays to summarize the status of the antenna, subreflector, and the Master Equatorial. The ACR software has two major functions. First, it performs all of the steps required to accurately point the antenna (and subreflector and Master Equatorial) at the spacecraft (or celestial target). This involves controlling the antenna/ subreflector/Master-Equatorial hardware, initiating and monitoring the correct sequence of operations, calculating the position of the spacecraft relative to the antenna, executing the real-time servo control algorithm to maintain the correct position, and

  5. 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.

  6. 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.

  7. The HDACi Panobinostat Shows Growth Inhibition Both In Vitro and in a Bioluminescent Orthotopic Surgical Xenograft Model of Ovarian Cancer

    PubMed Central

    Helland, Øystein; Popa, Mihaela; Bischof, Katharina; Gjertsen, Bjørn Tore; McCormack, Emmet; Bjørge, Line

    2016-01-01

    Background In most epithelial ovarian carcinomas (EOC), epigenetic changes are evident, and overexpression of histone deacetylases (HDACs) represents an important manifestation. In this study, we wanted to evaluate the effects of the novel HDAC inhibitor (HDACi) panobinostat, both alone and in combination with carboplatin, on ovarian cancer cell lines and in a murine bioluminescent orthotopic surgical xenograft model for EOC. Methods The effects of panobinostat, both alone and in combination with carboplatin, on proliferation and apoptosis in ovarian cancer cell lines, were evaluated using colony and WST-1 assays, Hoechst staining and flow cytometry analysis. In addition, mechanisms were characterised by western blotting and phosphoflow analysis. Immuno-deficient mice were engrafted orthotopically with SKOV-3luc+ cells and serial bioluminescence imaging monitored the effects of treatment with panobinostat and/or carboplatin and/or surgery. Survival parameters were also measured. Results Panobinostat treatment reduced cell growth and diminished cell viability, as shown by the induced cell cycle arrest and apoptosis in vitro. We observed increased levels of cleaved PARP and caspase-3, downregulation of cdc2 protein kinase, acetylation of H2B and higher pH2AX expression. The combined administration of carboplatin and panobinostat synergistically increased the anti-tumour effects compared to panobinostat or carboplatin treatment alone. In our novel ovarian cancer model, the mice showed significantly higher rates of survival when treated with panobinostat, carboplatin or a combination of both, compared to the controls. Panobinostat was as efficient as carboplatin regarding prolongation of survival. No significant additional effect on survival was observed when surgery was combined with carboplatin/panobinostat treatment. Conclusions Panobinostat demonstrates effective in vitro growth inhibition in ovarian cancer cells. The efficacy of panobinostat and carboplatin was

  8. Hybrid SPECT/CT evaluation of dual ectopia of thyroid in the absence of orthotopic thyroid gland.

    PubMed

    Harisankar, Chidambaram Natrajan Balasubramanian; Preethi, Govindababu Rajalakshmi; George, Mv

    2012-06-01

    Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is present at a location other than its usual site. The prevalence of ETT is approximately 1 per 100,000 to 300,000 persons and is reported to occur in 1 of 4000 to 8000 patients with thyroid disease. Multiple ectopia of the thyroid is extremely rare, with fewer than 35 cases published in literature to date. We report a 4-year-old girl with euthyroid and dual ectopia of thyroid without orthotopic thyroid gland. The role of hybrid SPECT/CT in the localization of the sites of ETT is also highlighted. PMID:22614198

  9. P08.10SINGLE BRAIN METASTASIS 9 YEARS AFTER ORTHOTOPIC LIVER TRANSPLANT WITH HISTOLOGICAL NEGATIVE EXPIANTED LIVER: CASE REPORT

    PubMed Central

    Fornaro, R.; Agnoletti, A.; Specchia, F.M. Calamo; Garbossa, D.; Lanotte, M.; Ducati, A.

    2014-01-01

    We describe the case of a 67 years old man, that underwent orthotopic liver transplant (OLT) in 2004 for cirrhosis. Native liver hystological examination was negative for focal hepatocarcinoma (HCC) areas. In 2008, during regular follow up, pulmonary lesions were found and diagnosed as hepatocarcinoma metastasis.In 2013, patient accused vertigo and dizziness: neuroimaging showed a cerebellar lesion. Hystological diagnosis was HCC metastases. The peculiarity is the onset of lung metastasis after transplant, with negative analysis on native liver, and brain metastasis after stable disease. This case is also relevant due to long survival related to the unavailability of many oncologic therapies in transplanted patients.

  10. Using your shoulder after replacement surgery

    MedlinePlus

    Joint replacement surgery - using your shoulder; Shoulder replacement surgery - after ... You have had shoulder replacement surgery to replace the bones of your shoulder joint with artificial parts. The parts include a stem made of metal and a ...

  11. Replacement Cost of Domestic Crude

    1994-12-01

    The DEEPWATER model forecasts the replacement cost of domestic crude oil for 13 offshore regions in the lower 48 states. The replacement cost of domestic crude oil is the constant or levelized selling price that will recover the full expense of exploration, development, and productions with a reasonable return on capital.

  12. Dialogue Replacement for Student Productions.

    ERIC Educational Resources Information Center

    Hank, Stephen

    1997-01-01

    Argues that film students should be taught how dialog replacement fits into overall engineering of a sound track--replacing dialog offers advantages to the student filmmaker that can enhance a less than stellar performance. States that skills such as foley artistry, postsynchronization of sound effects, and sound track engineering are as important…

  13. Percutaneous Valve Replacement: Significance of Different Delivery Systems In Vitro and In Vivo

    SciTech Connect

    Attmann, Tim; Lutter, Georg Quaden, Rene; Jahnke, Thomas; Rumberg, Kristin; Cremer, Jochen; Muller-Hulsbeck, Stefan

    2006-06-15

    Background and purpose. Percutaneous heart valve replacement is an exciting growing field in cardiovascular medicine yet still with some major problems. Only sophisticated improvement of the instruments could make it a real alternative to conventional surgery. Therefore, the aim of this study was to evaluate different delivery devices for percutaneous heart valve replacement in vitro and in vivo. Methods. A catheter prototype designed by our group, and two commercially available devices for the delivery of esophageal stents and aortic endoprostheses, were tested. After in vitro experiments, an ovine animal model of transfemoral pulmonary valve implantation was established using biological valved self-expanding stents. Only the delivery device for aortic endografts (Medtronic, Talent, Santa Rosa, CA, USA) allowed fast in vitro procedures without material fatigue. This device was chosen for the in vivo tests. Results. Technical success was achieved in 9 of 10 animals (90%). One animal died after perforation of the ventricular wall. Orthotopic pulmonary placement was performed in 6 animals and intentional supravalvular valved stent placement in 3 animals. Conclusions. An adequate in vitro model for this evolving field of interventional heart valve replacement is presented. Furthermore, the present study pinpoints the key characteristics that are mandatory for a delivery system in percutaneous pulmonary valve implantation. With regard to the delivery device's ductility observed during this 'venous' study, an approach to transfemoral aortic valve implantation seems feasible.

  14. [Detubularized U-shaped enterocystoplasty after cystoprostatectomy].

    PubMed

    el Mrini, M; Aboutaieb, R; el Fatimi, A; Sarf, I; Joual, A; Bennani, S; Elmoussaoui, A; Benjelloun, S

    1996-01-01

    We reviewed the charts of 58 patients who underwent orthotopic bladder replacement after total cystoprostatectomy for muscle invasive bladder cancer. Mean age was 56 years. As described by Camey, 60 centimetres of small bowel, are isolated, detubularised then folded upon itself to form a U shaped reservoir, which is anastomosed to the urethra. Death occurred in 5%. Urologic complications observed were: urinary leakage (15%), ureteral reflux (6.8%), ureteral stenosis (8.6%) and stones of the neobladder (5.1%). 64.2% of the patients were immediately continent during the day. Nocturnal continence was obtained for 50% immediately and for 80% three months postoperatively. Detubularised and U shaped cystoplasty achieve a low pressure reservoir, with protection of the upper urinary tract, and a diurnal continence. Nocturnal continence is achieved later.

  15. Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging.

    PubMed

    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/100 μm2 within 10 μm from the nearest source and few nanoparticles beyond 50 μm, respectively. The spleen had 35.5 ± 9.3 particles/100 μm2 within 10 μm with penetration also limited to 50 μm. For SGN, the liver showed 31.1 ± 4.1 particles/100 μm2 within 10 μm of the nearest source with penetration hindered beyond 30 μm. The spleen and tumor showed uptake of 22.1 ± 6.2 and 15.8 ± 6.1 particles/100 μm2 within 10 μm, 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

  16. Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation

    PubMed Central

    Feliciano, Helene; Martin, David; Regamey, Julien; Tozzi, Piergiorgio; Meyer, Philippe; Hullin, Roger

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:27669015

  17. 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

  18. Porous poly(propylene fumarate) foam coating of orthotopic cortical bone grafts for improved osteoconduction.

    PubMed

    Lewandrowski, Kai-Uwe; Bondre, Shrikar; Hile, David D; Thompson, Benjamin M J; Wise, Donald L; Tomford, William W; Trantolo, Debra J

    2002-12-01

    A porous biodegradable scaffold coating for perforated and demineralized cortical bone allografts could maintain immediate structural recovery and subsequently allow normal healing and remodeling by promoting bony ingrowth and avoiding accelerated graft resorption. This new type of osteoconductive surface modification should improve allograft incorporation by promoting new bone growth throughout the biodegradable scaffold, hence encasing the graft with the recipient's own bone. We investigated the feasibility of augmenting orthotopically transplanted cortical bone grafts with osteoconductive biodegradable polymeric scaffold coatings. Five types of bone grafts were prepared: type I, untreated fresh-frozen cortical bone grafts (negative control); type II, perforated and partially demineralized cortical bone grafts without additional coating (positive control); type III, perforated and partially demineralized cortical bone coated with a low-porosity poly(propylene fumarate) (PPF) foam; type IV, perforated and partially demineralized cortical bone coated with a medium-porosity PPF foam; and type V, perforated and partially demineralized cortical bone coated with a high-porosity PPF foam. Grafts were implanted into the rat tibial diaphysis. Fixation was achieved with an intramedullary threaded K-wire. Two sets of animals were operated on. Animals were killed in groups of eight with one set being killed 12 weeks, and the other 16 weeks, postoperatively. Radiographic, histologic, and histomorphometric analyses of grafts showed that the amount of new bone forming around the foam-coated grafts was significantly higher than that in the type I control group (uncoated) or that in type II group (perforated and partially demineralized cortical bone grafts). Although all foam formulations appeared initially equally osteoconductive, histologic evaluation of medium-porosity PPF foam-based coatings appeared to result in a sustained response 16 weeks postoperatively. Significant

  19. Inherently multimodal nanoparticle-driven tracking and real-time delineation of orthotopic prostate tumors and micrometastases.

    PubMed

    Liu, Tracy W; Macdonald, Thomas D; Jin, Cheng S; Gold, Joseph M; Bristow, Robert G; Wilson, Brian C; Zheng, Gang

    2013-05-28

    Prostate cancer is the most common cancer among men and the second cause of male cancer-related deaths. There are currently three critical needs in prostate cancer imaging to personalize cancer treatment: (1) accurate intraprostatic imaging for multiple foci and extra-capsular extent; (2) monitoring local and systemic treatment response and predicting recurrence; and (3) more sensitive imaging of occult prostate cancer bone metastases. Recently, our lab developed porphysomes, inherently multimodal, all-organic nanoparticles with flexible and robust radiochemistry. Herein, we validate the first in vivo application of (64)Cu-porphysomes in clinically relevant orthotopic prostate and bony metastatic cancer models. We demonstrate clear multimodal delineation of orthotopic tumors on both the macro- and the microscopic scales (using both PET and fluorescence) and sensitively detected small bony metastases (<2 mm). The unique and multifaceted properties of porphysomes offers a promising all-in-one prostate cancer imaging agent for tumor detection and treatment response/recurrence monitoring using both radionuclide- and photonic-based strategies.

  20. Lentivirus IL-10 gene therapy down-regulates IL-17 and attenuates mouse orthotopic lung allograft rejection.

    PubMed

    Hirayama, S; Sato, M; Loisel-Meyer, S; Matsuda, Y; Oishi, H; Guan, Z; Saito, T; Yeung, J; Cypel, M; Hwang, D M; Medin, J A; Liu, M; Keshavjee, S

    2013-06-01

    The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation. PMID:23601206

  1. Orthotopic genital sparing radical cystectomy in pre-menopausal women with muscle-invasive bladder carcinoma: A prospective study

    PubMed Central

    Moursy, Essam ElDin S.; Eldahshoursy, Mohammed Z.; Gamal, Wael M.; Badawy, Abdelbasset A.

    2016-01-01

    Introduction: Invasive cancer bladder is a life-threatening disease that is best treated with radical cystectomy and a suitable urinary diversion. The aim of this study was to evaluate the oncological outcome, voiding and sexual functions after genital sparing radical cystectomy with orthotopic bladder reconstruction in pre-menopausal women with bladder cancer. Materials and Methods: 18 pre-menopausal women who underwent radical cystectomy and orthotopic urinary diversion with preservation of genital organs were included for this study. The patients were followed-up clinically and radiologically to assess their oncological outcome in addition to their voiding and sexual function. Results: Mean age of the patients was 37.8 years, and the median follow-up after surgery was 70 months. One patient was lost to follow-up at 12 months post-operatively. The surgery was completed as planned in all patients, with a mean operative time of 290 min and an average blood loss of 750 mL. 14 patients were able to void satisfactorily, being continent day and night, while four patients needed clean intermittent catheterization. Sexual life remained unchanged in 15 cases, while three patients reported dysparunea. Till the last follow-up, there was no local recurrence while distant metastases were detected in three cases, two of whom died. Conclusions: Genital sparing cystectomy is a valid option for managing carefully selected women with muscle-invasive bladder cancer with good functional and sexual outcomes. PMID:26941498

  2. Inherently Multimodal Nanoparticle-Driven Tracking and Real-Time Delineation of Orthotopic Prostate Tumors and Micrometastases

    PubMed Central

    2013-01-01

    Prostate cancer is the most common cancer among men and the second cause of male cancer-related deaths. There are currently three critical needs in prostate cancer imaging to personalize cancer treatment: (1) accurate intraprostatic imaging for multiple foci and extra-capsular extent; (2) monitoring local and systemic treatment response and predicting recurrence; and (3) more sensitive imaging of occult prostate cancer bone metastases. Recently, our lab developed porphysomes, inherently multimodal, all-organic nanoparticles with flexible and robust radiochemistry. Herein, we validate the first in vivo application of 64Cu-porphysomes in clinically relevant orthotopic prostate and bony metastatic cancer models. We demonstrate clear multimodal delineation of orthotopic tumors on both the macro- and the microscopic scales (using both PET and fluorescence) and sensitively detected small bony metastases (<2 mm). The unique and multifaceted properties of porphysomes offers a promising all-in-one prostate cancer imaging agent for tumor detection and treatment response/recurrence monitoring using both radionuclide- and photonic-based strategies. PMID:23544841

  3. Applicable apparent diffusion coefficient of an orthotopic mouse model of gastric cancer by improved clinical MRI diffusion weighted imaging

    PubMed Central

    Sun, Jia; Zhang, Xiao-Peng; Li, Xiao-Ting; Tang, Lei; Cui, Yong; Zhang, Xiao-Yan; Sun, Ying-Shi

    2014-01-01

    In vivo imaging studies in animal models are hindered by variables that contribute to poor image quality and measurement reliability. As such we sought to improve the diffusion coefficient (ADC) of an orthotopic mouse model of gastric cancer in diffusion-weighted images (DWI) using alginate moulding and Ultrasonic coupling medium. BGC-823 human gastric cancer cells were subcutaneously injected into the abdomen of nude mice and 1 mm3 primary tumour was orthotopically transplanted. Alginate and coupling medium were applied to the mice and MRI (T2 and DWI) was performed for 6 weeks. Regions of interest (ROI) were drawn and liver and tumour ADC were evaluated. Using alginate moulding, the mean quality total score of DW imaging was 8.53; however, in control animals this value was 5.20 (p < 0.001). The coefficient of variation of ADC of liver in experimental and control groups were 0.071 and 0.270 (p < 0.001), respectively, suggesting this method may be helpful for DWI studies of important human diseases such as gastric cancer. PMID:25123166

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

    SciTech Connect

    Jarmila, Lastovickova 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 treating 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.

  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.

  6. High Resolution Ultrasound and Photoacoustic Imaging of Orthotopic Lung Cancer in Mice: New Perspectives for Onco-Pharmacology

    PubMed Central

    Sobilo, Julien; Le Mée, Marilyne; Rétif, Stéphanie; Natkunarajah, Sharuja; Lerondel, Stéphanie; Le Pape, Alain

    2016-01-01

    Objectives We have developed a relevant preclinical model associated with a specific imaging protocol dedicated to onco-pharmacology studies in mice. Materials and Methods We optimized both the animal model and an ultrasound imaging procedure to follow up longitudinally the lung tumor growth in mice. Moreover we proposed to measure by photoacoustic imaging the intratumoral hypoxia, which is a crucial parameter responsible for resistance to therapies. Finally, we compared ultrasound data to x-ray micro computed tomography and volumetric measurements to validate the relevance of this approach on the NCI-H460 human orthotopic lung tumor. Results This study demonstrates the ability of ultrasound imaging to detect and monitor the in vivo orthotopic lung tumor growth by high resolution ultrasound imaging. This approach enabled us to characterize key biological parameters such as oxygenation, perfusion status and vascularization of tumors. Conclusion Such an experimental approach has never been reported previously and it would provide a nonradiative tool for assessment of anticancer therapeutic efficacy in mice. Considering the absence of ultrasound propagation through the lung parenchyma, this strategy requires the implantation of tumors strictly located in the superficial posterior part of the lung. PMID:27070548

  7. Fracture After Total Hip Replacement

    MedlinePlus

    ... er Total Hip Replacement cont. • Dislocation • Limb length inequality • Poor fracture healing • Repeat fracture • Lack of in- ... Surgeons (AAOS). To learn more about your orthopaedic health, please visit orthoinfo.org. Page ( 5 ) AAOS does ...

  8. When to Replace a Prosthesis

    MedlinePlus

    Donate Fundraise Connect Contact Us Materiales en español Amputee Coalition Navigation HOME WHO WE ARE About Us ... Advisory Committee Connect With Us! STORE CALENDAR SEARCH Amputee Coalition > Limb Loss Resource Center > When to Replace ...

  9. Meal replacements and energy balance.

    PubMed

    Heymsfield, Steven B

    2010-04-26

    Induction and maintenance of a period of negative energy balance are required for overweight and obese subjects to lose weight. Meal replacements, particularly in beverage form, have now evolved as part of the "toolbox" used by researchers and clinicians to achieve negative energy balance. This overview traces the historical development of beverage meal replacements, reviews key studies supporting their clinical efficacy, and examines concerns related to their safe use. This collective information supports the view that meal replacements, particularly in beverage form, are now an effective and safe component for use in the clinical setting. Further studies are needed to identify those subjects most likely to benefit from use of meal replacements as part of their comprehensive weight control program.

  10. 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.

  11. Establishment of an orthotopic transplantation tumor model in nude mice using a drug-resistant human ovarian cancer cell line with a high expression of c-Kit.

    PubMed

    Yi, Cunjian; Zhang, Lei; Li, Li; Liu, Xiangqiong; Ling, Shengrong; Zhang, Fayun; Liang, Wei

    2014-12-01

    The resistance of ovarian cancer to platinum-based chemotherapy is a critical issue in the clinical setting. The present study aimed to establish animal models to replicate this clinical condition, as well as to investigate the resistance mechanisms of ovarian cancer. A cisplatin (DDP)-resistant human ovarian cancer cell line, SKOV3/DDP, was screened, validated and injected subcutaneously into the neck of female nude mice. Following tumor establishment, the tumor was collected and cut into small sections, which were subsequently implanted into the ovaries of other nude mice. The growth of the orthotopic tumors was observed and the tumor-bearing mice were sacrificed and dissected. The orthotopic and metastatic tumor tissues were collected, sectioned, stained with hematoxylin and eosin and analyzed. In the present study, 16 nude mice underwent orthotopic transplantation surgery and a tumor model was successfully established in 14/16 of the mice, with an in situ tumor formation rate of 87.5%. Following euthanasia, a laparotomy demonstrated the tumor formation at the site of transplantation, as well as varying degrees of metastasis to additional organs and tissues. Therefore, the present study successfully established an orthotopic tumor transplantation model in nude mice using a c-Kit-positive DDP-resistant human ovarian cancer cell line. This model may represent a useful tool for investigating the resistance mechanism of ovarian cancer, as well as evaluating the efficacy of therapeutic strategies.

  12. An Oncolytic Vaccinia Virus Expressing the Human Sodium Iodine Symporter Prolongs Survival and Facilitates SPECT/CT Imaging in an Orthotopic Model of Malignant Pleural Mesothelioma

    PubMed Central

    Belin, Laurence J.; Ady, Justin W.; Lewis, Christina; Marano, Drew; Gholami, Sepideh; Mojica, Kelly; Eveno, Clarisse; Longo, Valerie; Zanzonico, Pat B.; Chen, Nanhai G.; Szalay, Aladar A.; Fong, Yuman

    2014-01-01

    Background The purpose of this original work is to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM). Methods Infectivity and cytotoxic effect of GLV-1h153 on mesothelioma cell lines of all histologic subtypes was assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice and treated with intrapleural GLV-1h153 and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on SPECT/CT after 131I administration. Results GLV-1h153 infected and killed all cell lines in a time and concentration dependent manner. Viral replication demonstrated over a 2.5 log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant reduction in tumor burden one week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusions Our results suggest GLV-1h153 is a promising therapeutic agent for MPM and warrants further investigation. PMID:23890748

  13. Replacing equipment due to obsolescence, fuel efficiency

    SciTech Connect

    Harbor, V.

    1982-08-23

    Southern Natural Gas' engine replacement program with regard to expansion problems, replacement justification, meeting requirements (e.g. FERC regulations), economics, and removal and replacement was examined. As a result of replacement, gas supplies are more plentiful; and due to increased load factors, the replacing of four 1,300-hp units is now under way.

  14. 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

  15. Optimization of station battery replacement

    NASA Astrophysics Data System (ADS)

    Jancauskas, J. R.; Shook, D. A.

    1994-08-01

    During a loss of ac power at a nuclear generating station (including diesel generators), batteries provide the source of power which is required to operate safety-related components. Because traditional lead-acid batteries have a qualified life of 20 years, the batteries must be replaced a minimum of once during a station's lifetime, twice if license extension is pursued, and more often depending on actual in-service dates and the results of surveillance tests. Replacement of batteries often occurs prior to 20 years as a result of systems changes caused by factors such as Station Blackout Regulations, control system upgrades, incremental load growth, and changes in the operating times of existing equipment. Many of these replacement decisions are based on the predictive capabilities of manual design basis calculations. The inherent conservatism of manual calculations may result in battery replacements occurring before actually required. Computerized analysis of batteries can aid in optimizing the timing of replacements as well as in interpreting service test data. Computerized analysis also provides large benefits in maintaining the as-configured load profile and corresponding design margins, while also providing the capability to quickly analyze proposed modifications and respond to internal and external audits.

  16. Homologous gene replacement in Physarum

    SciTech Connect

    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}1 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.

  17. Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.

    PubMed

    Weng, Ling-Ling; Xiang, Jian-Feng; Lin, Jin-Bo; Yi, Shang-Hui; Yang, Li-Tao; Li, Yi-Sheng; Zeng, Hao-Tao; Lin, Sheng-Ming; Xin, Dong-Wei; Zhao, Hai-Liang; Qiu, Shu-Qi; Chen, Tao; Zhang, Min-Guang

    2014-01-01

    Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy. PMID:25605207

  18. Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.

    PubMed

    Weng, Ling-Ling; Xiang, Jian-Feng; Lin, Jin-Bo; Yi, Shang-Hui; Yang, Li-Tao; Li, Yi-Sheng; Zeng, Hao-Tao; Lin, Sheng-Ming; Xin, Dong-Wei; Zhao, Hai-Liang; Qiu, Shu-Qi; Chen, Tao; Zhang, Min-Guang

    2014-01-01

    Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

  19. Circulating tumor cells are correlated with disease progression and treatment response in an orthotopic hepatocellular carcinoma model.

    PubMed

    Yan, Jun; Fan, Zhichao; Wu, Xiufeng; Xu, Min; Jiang, Jiahao; Tan, Changjun; Wu, Weizhong; Wei, Xunbin; Zhou, Jian

    2015-11-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent hematogenous metastasis. A minimally invasive diagnostic biomarker that can predict disease progression and treatment response would be of extraordinary benefit. Therefore, we have investigated whether the number of circulating tumor cells (CTCs) is correlated with disease progression and treatment response in HCC. Here we report that the number of CTCs, monitored by in vivo flow cytometry (IVFC), is strongly correlated with disease progression and treatment response in a highly metastatic orthotopic nude mouse model of green fluorescent protein (GFP)-labeled HCC. Sorafenib treatment reduces the number of CTCs significantly. The decreased number of CTCs is consistent with low lung metastasis. This study has demonstrated a considerable clinical value of CTCs as a biomarker in predicting disease progression and monitoring therapeutic efficacy in patients with HCC.

  20. Familial LCAT deficiency: from renal replacement to enzyme replacement.

    PubMed

    Stoekenbroek, R M; van den Bergh Weerman, M A; Hovingh, G K; Potter van Loon, B J; Siegert, C E H; Holleboom, A G

    2013-01-01

    Familial LCAT deficiency (FLD) is a recessive lipid disorder ultimately leading to end-stage renal disease (ESRD). We present two brothers with considerable variation in the age at which they developed ESRD. Kidney biopsies revealed both tubular and glomerular pathology. To date, no causal therapy is available, yet enzyme replacement therapy is in development. PMID:23412821

  1. Molecular replacement: tricks and treats

    SciTech Connect

    Abergel, Chantal

    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% of 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.

  2. APACHE IV Is Superior to MELD Scoring System in Predicting Prognosis in Patients after Orthotopic Liver Transplantation

    PubMed Central

    Zhang, Xianling; Liu, Yuan; Yan, Jun; Li, Tiehua; Hu, Ailing

    2013-01-01

    This study aims to compare the efficiency of APACHE IV with that of MELD scoring system for prediction of the risk of mortality risk after orthotopic liver transplantation (OLT). A retrospective cohort study was performed based on a total of 195 patients admitted to the ICU after orthotopic liver transplantation (OLT) between February 2006 and July 2009 in Guangzhou, China. APACHE IV and MELD scoring systems were used to predict the postoperative mortality after OLT. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow C statistic were used to assess the discrimination and calibration of APACHE IV and MELD, respectively. Twenty-seven patients died during hospitalization with a mortality rate of 13.8%. The mean scores of APACHE IV and MELD were 42.32 ± 21.95 and 18.09 ± 10.55, respectively, and APACHE IV showed better discrimination than MELD; the areas under the receiver operating characteristic curve for APACHE IV and MELD were 0.937 and 0.694 (P < 0.05 for both models), which indicated that the prognostic value of APACHE IV was relatively high. Both models were well-calibrated (The Hosmer-Lemeshow C statistics were 1.568 and 6.818 for APACHE IV and MELD, resp.; P > 0.05 for both). The respective Youden indexes of APACHE IV, MELD, and combination of APACHE IV with MELD were 0.763, 0.430, and 0.545. The prognostic value of APACHE IV is high but still underestimates the overall hospital mortality, while the prognostic value of MELD is poor. The function of the APACHE IV is, thus, better than that of the MELD. PMID:24348682

  3. APACHE IV is superior to MELD scoring system in predicting prognosis in patients after orthotopic liver transplantation.

    PubMed

    Hu, Yueyun; Zhang, Xianling; Liu, Yuan; Yan, Jun; Li, Tiehua; Hu, Ailing

    2013-01-01

    This study aims to compare the efficiency of APACHE IV with that of MELD scoring system for prediction of the risk of mortality risk after orthotopic liver transplantation (OLT). A retrospective cohort study was performed based on a total of 195 patients admitted to the ICU after orthotopic liver transplantation (OLT) between February 2006 and July 2009 in Guangzhou, China. APACHE IV and MELD scoring systems were used to predict the postoperative mortality after OLT. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow C statistic were used to assess the discrimination and calibration of APACHE IV and MELD, respectively. Twenty-seven patients died during hospitalization with a mortality rate of 13.8%. The mean scores of APACHE IV and MELD were 42.32 ± 21.95 and 18.09 ± 10.55, respectively, and APACHE IV showed better discrimination than MELD; the areas under the receiver operating characteristic curve for APACHE IV and MELD were 0.937 and 0.694 (P < 0.05 for both models), which indicated that the prognostic value of APACHE IV was relatively high. Both models were well-calibrated (The Hosmer-Lemeshow C statistics were 1.568 and 6.818 for APACHE IV and MELD, resp.; P > 0.05 for both). The respective Youden indexes of APACHE IV, MELD, and combination of APACHE IV with MELD were 0.763, 0.430, and 0.545. The prognostic value of APACHE IV is high but still underestimates the overall hospital mortality, while the prognostic value of MELD is poor. The function of the APACHE IV is, thus, better than that of the MELD.

  4. Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma.

    PubMed

    Gatesman Ammer, Amanda; Hayes, Karen E; Martin, Karen H; Zhang, Lingqing; Spirou, George A; Weed, Scott A

    2011-07-25

    Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1(nu/nu) mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

  5. Pulmonary targeting microparticulate camptothecin delivery system: anti-cancer evaluation in a rat orthotopic lung cancer model

    PubMed Central

    Chao, Piyun; Deshmukh, Manjeet; Kutscher, Hilliard L.; Gao, Dayuan; Sundara Rajan, Sujata; Hu, Peidi; Laskin, Debra L.; Stein, Stanley; Sinko, Patrick J.

    2013-01-01

    Large (>6 µm) rigid microparticles (MPs) become passively entrapped within the lungs following intravenous injection making them an attractive and highly efficient alternative to inhalation for pulmonary delivery. In the current studies, PEGylated 6 μm polystyrene MPs with multiple copies of the norvaline (Nva) α-amino acid prodrug of camptothecin (CPT) were prepared. Surface morphology was characterized using a scanning electron microscope (SEM). CPT was released from the CPT-Nva-MPs over 24 hours in rat plasma at 37°C. In vivo CPT plasma concentrations were low (~1 ng/mL or less) and constant over a period of 4 days after a single intravenous injection of CPT-Nva-MPs as compared to high but short-lived systemic exposures after an IV injection of free CPT. This suggests that sustained local CPT concentrations were achieved in the lung after administration of the MP delivery system. Anti-cancer efficacy was evaluated in an orthotopic lung cancer animal model and compared to a bolus injection of CPT. Animals receiving either free CPT (2 mg/kg) or CPT-Nva-MPs (0.22 mg/kg CPT, 100 mg/kg MPs) were found to have statistically significant smaller areas of lung cancer (P<0.05, P<0.01, respectively) than untreated animals. In addition, 40% of the animals receiving CPT-Nva-MPs were found to be free of cancer. The CPT dose using targeted MPs was ten fold lower than after IV injection of free CPT but was more effective in reducing the amount of cancerous areas. In conclusion, CPT-Nva-MPs were able to achieve effective local lung and low systemic CPT concentrations at a dose that was ten times lower than systemically administered CPT resulting in a significant improvement in anticancer efficacy in an orthotopic rat model of lung cancer. PMID:19966540

  6. Imaging Hypoxia in Orthotopic Rat Liver Tumors with Iodine 124–labeled Iodoazomycin Galactopyranoside PET1

    PubMed Central

    Riedl, Christopher C.; Brader, Peter; Zanzonico, Pat B.; Chun, Yun Shin; Woo, Yanghee; Singh, Paramjeet; Carlin, Sean; Wen, Bixiu; Ling, C. Clifton; Hricak, Hedvig; Fong, Yuman

    2008-01-01

    Purpose: To evaluate iodine 124 (124I)-labeled iodoazomycin galactopyranoside (IAZGP) positron emission tomography (PET) in the detection of hypoxia in an orthotopic rat liver tumor model by comparing regions of high 124I-IAZGP uptake with independent measures of hypoxia and to determine the optimal time after injection to depict hypoxia. Materials and Methods: The institutional animal care and use committee approved this study. Morris hepatoma tumors were established in the livers of 15 rats. Tumor oxygenation was measured in two rats with a fluorescence fiberoptic oxygen probe. 124I-IAZGP was coadministered with the established hypoxia markers pimonidazole and EF5 in nine rats; 12-hour PET data acquisition was performed 24 hours later. Tumor cryosections were analyzed with immunofluorescence and autoradiography. In the four remaining rats, serial 20- and 60-minute PET data acquisition was peformed up to 48 hours after tracer administration. Results: Oxygen probe measurements showed severe hypoxia (<1 mm Hg) distributed evenly throughout tumor tissue. Analysis of cryosections showed diffuse homogeneous uptake of 124I-IAZGP throughout all tumors. The 124I-IAZGP distribution correlated positively with pimonidazole (r = 0.78) and EF5 (r = 0.76) distribution. Tracer uptake in tumors was detectable with PET after 24 hours in seven of nine rats. In rats that underwent serial PET, tumor-to-liver contrast was sufficient to enable detection of hypoxia between 6 and 48 hours after tracer administration. The optimal ratio between signal intensity and tumor-to-liver contrast occurred 6 hours after tracer administration. Conclusion: Regions of high 124I-IAZGP uptake in orthotopic rat liver tumors are consistent with independent measures of hypoxia; visualization of hypoxia with 124I-IAZGP PET is optimal 6 hours after injection. © RSNA, 2008 PMID:18641253

  7. 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.

  8. Replaceable Sleeve Protects Welder Coil

    NASA Technical Reports Server (NTRS)

    Baker, W. L.; Simpson, C., E.

    1983-01-01

    New replaceable carbon insert for deflection coil in electron-beam welder promises to decrease maintenance costs. Inserts made from materials other than carbon (not yet tried) are less expensive, thus reducing costs even further. With carbon insert, deflection coils last longer and are easier to maintain.

  9. Testing of Replacement Bag Material

    SciTech Connect

    Laurinat, J.E.

    1998-11-03

    Recently, the FB-Line bagout material was changed to simplify the processing of sand, slag, and crucible.The results of the strength tests and the outgassing measurements and calculations demonstrate that the proposed replacement nylon bag materials (HRMP and orange anti-static material) are acceptable substitutes for LDPE and the original nylon with respect to mechanical properties.

  10. Will peanut hulls replace oil

    SciTech Connect

    Not Available

    1980-12-01

    A low-cost, fast-curing wood adhesive has been recently developed by the University of Georgia, in which up to 80% of the petroleum ingredients can be replaced with a substance extracted from peanut hulls. An outline of the process is given.

  11. [Organ replacement therapy - renal replacement therapy in intensive care medicine].

    PubMed

    Kraus, Daniel; Wanner, Christoph

    2016-09-01

    Critically ill patients who are treated in an intensive care unit are at increased risk of developing acute renal failure. Every episode of renal failure decreases life expectancy. However, acute renal failure is no longer an immediate cause of death because renal function can be substituted medically and mechanically, by the use of renal replacement therapy. Hemodialysis and hemofiltration are the 2 fundamental modalities of renal replacement therapy and may be performed intermittently or continuously. The decision for one particular therapy has to be made for each patient individually. Peritoneal dialysis is an alternative treatment for acute renal failure, but is not available for immediate use in most centers. Contrast media and rhabdomyolysis are 2 common causes of toxic renal failure in the intensive care unit. However, they cannot be prevented by hemodialysis. PMID:27631449

  12. Urinary diversion after cystectomy: An Indian perspective

    PubMed Central

    Jain, Deepak; Raghunath, S. K.; Khanna, Samir; Kumar, Prem; Rawal, Sudhir

    2008-01-01

    Radical cystectomy remains the standard treatment for muscle-invasive carcinoma bladder. Various methods have been described for the urinary diversion. In the last 150 years urinary diversion has evolved from cutaneous ureterostomy to the orthotopic neobladder. Especially during the last 20 years, much advancement has been made. We hereby have reviewed the current approaches being used at different centers in India. We have also analyzed the evolution of diversion from conduit to the orthotopic substitution at our center. PMID:19468368

  13. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    PubMed

    Tabata, Minoru

    2016-03-01

    Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR.

  14. Hurricane intensity and eyewall replacement.

    PubMed

    Houze, Robert A; Chen, Shuyi S; Smull, Bradley F; Lee, Wen-Chau; Bell, Michael M

    2007-03-01

    Observations made during the historic 2005 hurricane season document a case of "eyewall replacement." Clouds outside the hurricane eyewall coalesce to form a new eyewall at a greater radius from the storm center, and the old eyewall dies. The winds in the new eyewall are initially weaker than those in the original eyewall, but as the new eyewall contracts, the storm reintensifies. Understanding this replacement mechanism is vital to forecasting variations in hurricane intensity. Processes in the "moat" region between the new and old eyewall have been particularly unclear. Aircraft data now show that the moat becomes dynamically similar to the eye and thus is converted into a region inimical to survival of the inner eyewall. We suggest that targeting aircraft to key parts of the storm to gain crucial input to high-resolution numerical models can lead to improvements in forecasting hurricane intensity.

  15. Replacement element for automobile thermostat

    SciTech Connect

    Ferrari, W.

    1988-06-07

    This patent describes a thermostat replacement element for use in a cooling system in which a continuous stream of coolant normally flows from a radiator through a thermostat to an engine. The thermostat is mounted within a mounting cavity and permits maximum flow of coolant through the cooling system when in an open position. The replacement element comprises a disc-shaped member having a diameter substantially corresponding to the diameter of the mounting cavity. The member is provided with apertures of a predetermined size to permit flow of coolant therethrough at a rate generally corresponding to the rate of flow of coolant through the thermostat when the thermostat is in an open position.

  16. Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models

    PubMed Central

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.

    2015-01-01

    Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis. PMID:26375054

  17. Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models.

    PubMed

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-10-13

    Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis.

  18. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  19. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder.

  20. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  1. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder.

  2. Fluorescent-Antibody Targeting of Insulin-Like Growth Factor-1 Receptor Visualizes Metastatic Human Colon Cancer in Orthotopic Mouse Models

    PubMed Central

    Park, Jeong Youp; Murakami, Takashi; Lee, Jin Young; Zhang, Yong; Hoffman, Robert M.; Bouvet, Michael

    2016-01-01

    Fluorescent-antibody targeting of metastatic cancer has been demonstrated by our laboratory to enable tumor visualization and effective fluorescence-guided surgery. The goal of the present study was to determine whether insulin-like growth factor-1 receptor (IGF-1R) antibodies, conjugated with bright fluorophores, could enable visualization of metastatic colon cancer in orthotopic nude mouse models. IGF-1R antibody (clone 24–31) was conjugated with 550 nm, 650 nm or PEGylated 650 nm fluorophores. Subcutaneous, orthotopic, and liver metastasis models of colon cancer in nude mice were targeted with the fluorescent IGF-1R antibodies. Western blotting confirmed the expression of IGF-1R in HT-29 and HCT 116 human colon cancer cell lines, both expressing green fluorescent protein (GFP). Labeling with fluorophore-conjugated IGF-1R antibody demonstrated fluorescent foci on the membrane of colon cancer cells. Subcutaneously- and orthotopically-transplanted HT-29-GFP and HCT 116-GFP tumors brightly fluoresced at the longer wavelengths after intravenous administration of fluorescent IGF-1R antibodies. Orthotopically-transplanted HCT 116-GFP tumors were brightly labeled by fluorescent IGF-1R antibodies such that they could be imaged non-invasively at the longer wavelengths. In an experimental liver metastasis model, IGF-1R antibodies conjugated with PEGylated 650 nm fluorophores selectively highlighted the liver metastases, which could then be non-invasively imaged. The IGF-1R fluorescent-antibody labeled liver metastases were very bright compared to the normal liver and the fluorescent-antibody label co-located with green fluorescent protein (GFP) expression of the colon cancer cells. The present study thus demonstrates that fluorophore-conjugated IGF-1R antibodies selectively visualize metastatic colon cancer and have clinical potential for improved diagnosis and fluorescence-guided surgery. PMID:26731105

  3. Bufalin Inhibits HCT116 Colon Cancer Cells and Its Orthotopic Xenograft Tumor in Mice Model through Genes Related to Apoptotic and PTEN/AKT Pathways

    PubMed Central

    Wang, Jie; Chen, Chao; Wang, Shiying; Zhang, Yong; Yin, Peihao; Gao, Zhongxiang; Xu, Jie; Feng, Dianxu; Zuo, Qinsong; Zhao, Ronghua; Chen, Teng

    2015-01-01

    Aims. To investigate the anticolorectal cancer (CRC) effects of Bufalin, a bioactive polyhydroxysteroid from Venenum Bufonis, using HCT116 human CRC cell and an established orthotopic xenograft model in mice, and to explore the mechanisms of action. Material and Methods. Cultured HCT116 cells or BALB/c mice with orthotopic tumor were treated by Bufalin (positive control: 5-FU). Cell proliferation, apoptosis, and cycling were determined by MTT, Annexin V/PI staining, and flow cytometry, respectively. In mice, tumor inhibition rate and animal survival were calculated. The expressions of PTEN/phosphate-PTEN, AKT/phosphate-AKT, Bad, Bcl-xl, Bax, or Caspase-3 in cells and/or tumors were determined by Western blot or immunohistochemical staining. Results. Bufalin significantly inhibited cell proliferation and induced cell apoptosis and cycle arrest in a dose/time-dependent manner. In the animal model, Bufalin treatment resulted in significant inhibition of tumor growth and prolonged survival. In the Bufalin-treated cultured cells and/or xenograft tumors, the expressions of PTEN, Bad, Bax, and Caspase-3 were significantly increased, while p-AKT and Bcl-xL significantly decreased. Conclusions. Our results indicate that Bufalin inhibit cell proliferation and orthotopic tumor growth by inducing cell apoptosis through the intrinsic apoptotic pathway, which is of pivotal significance in the identification of an anticancer drug that may synergize with Bufalin. PMID:26770191

  4. 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.

  5. 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.

    PubMed

    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.

  6. Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model

    PubMed Central

    Shultz, Michael D.; Wilson, John D.; Fuller, Christine E.; Zhang, Jianyuan; Dorn, Harry C.

    2011-01-01

    Purpose: To demonstrate in an orthotopic xenograft brain tumor model that a functionalized metallofullerene (f-Gd3N@C80) can enable longitudinal tumor imaging and, when radiolabeled with lutetium 177 (177Lu) and tetraazacyclododecane tetraacetic acid (DOTA) (177Lu-DOTA-f-Gd3N@C80), provide an anchor to deliver effective brachytherapy. Materials and Methods: All experiments involving the use of mice were carried out in accordance with protocols approved by the institutional animal care and use committee. Human glioblastoma U87MG cells were implanted by using stereotactic procedures into the brains of 37 female athymic nude-Foxn1nu mice and allowed to develop into a tumor for 8 days. T1- and T2-weighted magnetic resonance (MR) imaging was performed in five mice. Biodistribution studies were performed in 12 mice at four time points over 7 days to evaluate gadolinium content. Survival studies involved 20 mice that received infusion of a nanoplatform by means of convection-enhanced delivery (CED) 8 days after tumor implantation. Mice in survival studies were divided into two groups: one comprised untreated mice that received f-Gd3N@C80 alone and the other comprised mice treated with brachytherapy that received 1.11 MBq of 177Lu-DOTA-f-Gd3N@C80. Survival data were evaluated by using Kaplan-Meier statistical methods. Results: MR imaging showed extended tumor retention (25.6% ± 1.2 of the infused dose at 52 days, confirmed with biodistribution studies) of the f-Gd3N@C80 nanoplatform, which enabled longitudinal imaging. Successful coupling of 177Lu to the f-Gd3N@C80 surface was achieved by using a bifunctional macrocyclic chelator. The extended tumor retention allowed for effective brachytherapy, as indicated by extended survival time (>2.5 times that of the untreated group) and histologic signs of radiation-induced tumor damage. Conclusion: The authors have developed a multimodal nanoplatform and have demonstrated longitudinal tumor imaging, prolonged intratumoral probe

  7. 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

  8. Solvent replacement for green processing.

    PubMed Central

    Sherman, J; Chin, B; Huibers, P D; Garcia-Valls, R; Hatton, T A

    1998-01-01

    The implementation of the Montreal Protocol, the Clean Air Act, and the Pollution Prevention Act of 1990 has resulted in increased awareness of organic solvent use in chemical processing. The advances made in the search to find "green" replacements for traditional solvents are reviewed, with reference to solvent alternatives for cleaning, coatings, and chemical reaction and separation processes. The development of solvent databases and computational methods that aid in the selection and/or design of feasible or optimal environmentally benign solvent alternatives for specific applications is also discussed. Images Figure 2 Figure 3 PMID:9539018

  9. Replacing London's cast iron mains

    SciTech Connect

    Thorne, A. ); Mathews, P. )

    1992-07-01

    This paper discusses the cast iron gas distribution systems that exist in many cities and contains considerable amounts of pipe that vary in age from 20 to 150 years. In many ways, cast iron is an excellent material. It is inherently corrosion resistant, easy to install and cheap. However, it is also brittle and smaller diameter cast iron pipe has a relatively low beam strength. This can lead, under some circumstances, to failure without external warning, with typically a full-circumferential failure. In congested areas this can lead to serious consequences. As a result, cast iron replacement programs are a common feature in such urban gas distribution systems.

  10. Anesthesia for bone replacement surgery

    PubMed Central

    Singh, Sunil; Singh, Shri Prakash; Agarwal, Jitendra K

    2012-01-01

    Advances in clinical medicine, improved understanding of pathophysiology, and the extensive application of medical technology have projected hitherto high risk and poor outcome surgical procedures into the category of routine and relatively good outcome surgeries. Bone replacement surgery is one amongst these and is wrought with a multitude of perioperative complexities. An understanding of these goes a long way in assisting in the final outcome for the patient. Here we present a review of the literature covering various issues involved during the different stages of the perioperative period. PMID:22557736

  11. Patellofemoral replacement: the third compartment.

    PubMed

    Hofmann, A A; McCandless, J B; Shaeffer, J F; Magee, T H

    2013-11-01

    Isolated patellofemoral arthritis is a common condition and there are varying opinions on the most effective treatments. Non-operative and operative treatments have failed to demonstrate effective long-term treatment for those in an advanced stage of the condition. Newer designs and increased technology in patellofemoral replacement (PFR) have produced more consistent outcomes. This has led to a renewed enthusiasm for this procedure. Newer PFR prostheses have addressed the patellar maltracking issues plaguing some of the older designs. Short-term results with contemporary prostheses and new technology are described here.

  12. Orthotopic animal model of pseudomyxoma peritonei: An in vivo model to test anti-angiogenic drug effects.

    PubMed

    Dohan, Anthony; Lousquy, Ruben; Eveno, Clarisse; Goere, Diane; Broqueres-You, Dong; Kaci, Rachid; Lehmann-Che, Jacqueline; Launay, Jean-Marie; Soyer, Philippe; Bonnin, Philippe; Pocard, Marc

    2014-07-01

    Pseudomyxoma peritonei (PMP) is an uncommon peritoneal mucinous carcinomatosis confined to the peritoneal cavity. The rarity of PMP in humans makes evaluation of the disease biological features and new therapeutic strategies difficult. Accordingly, there is a need for animal models of PMP. Human PMP tissue was i.p. grafted and grown into nude mice, then constituted into reliable and reproducible orthotopic models. Histological and immunostaining analysis was performed. Bevacizumab was injected twice a week either during tumor growth or after cytoreductive surgery. In vivo imaging of tumor angiogenesis was performed using barium sulfate or isolectin microangiography and Doppler ultrasonography of the superior mesenteric artery. Tumor angiogenesis was confirmed by the presence of tortuous vascular networks with high levels of expression of CD31, vascular endothelial cadherin, and desmin. Doppler ultrasonography of the superior mesenteric artery revealed a twofold increase in blood flow velocity compared with tumor-free mice (P < 0.001). Bevacizumab administration was correlated with the normalization of tumor vascularity when injected during tumor growth and with the stabilization of the histological and hemodynamic findings when injected after cytoreductive surgery. Our PMP models mimic human PMP. Our results confirmed the presence of tumor angiogenesis related to PMP growth. Our murine model allows researchers to actually bench test and evaluate, in preclinical studies, the efficacy of new therapeutic strategies and anti-angiogenic therapies. PMID:24814606

  13. Orthotopic animal model of pseudomyxoma peritonei: An in vivo model to test anti-angiogenic drug effects.

    PubMed

    Dohan, Anthony; Lousquy, Ruben; Eveno, Clarisse; Goere, Diane; Broqueres-You, Dong; Kaci, Rachid; Lehmann-Che, Jacqueline; Launay, Jean-Marie; Soyer, Philippe; Bonnin, Philippe; Pocard, Marc

    2014-07-01

    Pseudomyxoma peritonei (PMP) is an uncommon peritoneal mucinous carcinomatosis confined to the peritoneal cavity. The rarity of PMP in humans makes evaluation of the disease biological features and new therapeutic strategies difficult. Accordingly, there is a need for animal models of PMP. Human PMP tissue was i.p. grafted and grown into nude mice, then constituted into reliable and reproducible orthotopic models. Histological and immunostaining analysis was performed. Bevacizumab was injected twice a week either during tumor growth or after cytoreductive surgery. In vivo imaging of tumor angiogenesis was performed using barium sulfate or isolectin microangiography and Doppler ultrasonography of the superior mesenteric artery. Tumor angiogenesis was confirmed by the presence of tortuous vascular networks with high levels of expression of CD31, vascular endothelial cadherin, and desmin. Doppler ultrasonography of the superior mesenteric artery revealed a twofold increase in blood flow velocity compared with tumor-free mice (P < 0.001). Bevacizumab administration was correlated with the normalization of tumor vascularity when injected during tumor growth and with the stabilization of the histological and hemodynamic findings when injected after cytoreductive surgery. Our PMP models mimic human PMP. Our results confirmed the presence of tumor angiogenesis related to PMP growth. Our murine model allows researchers to actually bench test and evaluate, in preclinical studies, the efficacy of new therapeutic strategies and anti-angiogenic therapies.

  14. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC.

    PubMed

    Herz, Corinna; Hertrampf, Anke; Zimmermann, Stefan; Stetter, Nadine; Wagner, Meike; Kleinhans, Claudia; Erlacher, Miriam; Schüler, Julia; Platz, Stefanie; Rohn, Sascha; Mersch-Sundermann, Volker; Lamy, Evelyn

    2014-12-01

    In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level.

  15. 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.

  16. Percutaneous Treatment of Biliary Cast Syndrome After Orthotopic Liver Transplantation: Comparison of Mechanical Versus Hydraulic Rheolytic Cast Extraction

    SciTech Connect

    Lopez-Benitez, R. Wielpuetz, M. O. Bryant, M. G. H.; Ganten, Tom; Richter, G. M.; Flach, N. Hallscheidt, P. J.

    2011-10-15

    Purpose: Biliary cast syndrome (BCS) is the presence of casts within the intrahepatic or extrahepatic biliary system after orthotopic liver transplantation. Our work compares two percutaneous methods for BCS treatment: the mechanical cast-extraction technique (MCE) versus the hydraulic cast-extraction (HCE) technique using a rheolytic system. Materials and Methods: A total of 24 patients were included in the study. Six patients were referred for HCE, and 18 patients were treated with MCE. A statistically significant larger number of sessions was required in the MCE group (21.0, range 11 to 72 sessions) (p = 0.033). Results: Median therapy duration was shorter in the HCE group at 2.4 months (range 2 to 5) compared with 6.7 months (range 3 to 39) in the MCE group (p < 0.001). Both patient acceptance was better and costs for total therapy were 40% less in the HCE group. No significant differences where found concerning clinical and biochemical improvement or graft and patient survival. Conclusion: The use of the hydraulic rheolytic system decreased total therapy time, thereby decreasing the induced inflammation time of the biliary tree. A significant benefit of HCE has been observed in our patients when we compare our results with those of MCE.

  17. Inhibiting Integrin αvβ5 Reduces Ischemia-Reperfusion Injury in an Orthotopic Lung Transplant Model in Mice.

    PubMed

    Mallavia, B; Liu, F; Sheppard, D; Looney, M R

    2016-04-01

    Primary graft dysfunction after lung transplantation is the leading cause of morbidity and mortality in the immediate posttransplant period and is characterized by endothelial and epithelial barrier disruption and the leakage of protein-rich edema fluid. Integrins are cell surface receptors that have an important role in maintenance of the cell barrier, and inhibition of integrins, such as αvβ5, can diminish alveolar flooding in lung injury models. We hypothesized that inhibition of αvβ5 during donor lung cold ischemia would reduce endothelial permeability during reperfusion. Using an orthotopic single lung transplantation model with and without cold ischemia, donor lungs were perfused with αvβ5-blocking antibody (ALULA) or control antibody at the time of collection, followed by transplantation, 8 h of reperfusion, and the measurement of lung injury parameters. Prolonged cold ischemia (18 h) produced increases in extravascular lung water, protein permeability, and neutrophilic alveolitis and decreased oxygenation compared with lungs without cold ischemia. Perfusion of lungs with αvβ5 antibody versus control antibody protected donor lungs from injury and significantly improved oxygenation. In summary, αvβ5 integrin blockade protects from the development of ischemia-reperfusion lung injury and is a promising approach to preventing primary graft dysfunction in human lung transplant procedures.

  18. 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.

  19. In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer

    PubMed Central

    Pais, Adi; Gunanathan, Chidambaram; Margalit, Raanan; Biton, Inbal Eti; Yosepovich, Ady; Milstein, David; Degani, Hadassa

    2011-01-01

    Histological overexpression of the estrogen receptor α (ER) is a well established prognostic marker in breast cancer. Non-invasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patient's biopsies are problematic to obtain. This study focused on developing by in vivo magnetic resonance imaging (MRI) strategies to measure the level of ER expression in an orthotopic mouse model of human breast cancer. Specifically, novel ER-targeted contrast agents based on pyridine-tetra-acetate-Gd(III) chelate (PTA-Gd) conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd) were examined in ER-positive or ER-negative tumors. Detection of specific interactions of EPTA-Gd with ER were documented that could differentiate ER-positive and ER-negative tumors. In vivo competition experiments confirmed that the enhanced detection capability of EPTA-Gd was based specifically on ER targeting. In contrast, PTA-Gd acted as an extracellular probe that enhanced ER detection similarly in either tumor type, confirming a similar vascular perfusion efficiency in ER-positive and negative tumors in the model. Lastly, TPTA-Gd accumulated selectively in muscle and could not preferentially identify ER-positive tumors. Together, these results define a novel MRI probe that can permit selective noninvasive imaging of ER-positive tumors in vivo. PMID:22042793

  20. Role of CEACAM1, ECM, and mesenchymal stem cells in an orthotopic model of human breast cancer.

    PubMed

    Samineni, Sridhar; Glackin, Carlotta; Shively, John E

    2011-01-01

    Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is a morphogen in an in vitro model for lumen formation and plays a similar role in breast epithelial cells implanted in humanized mammary fat pads in NOD-SCID mice. Although extra cellular matrix alone is sufficient to stimulate lumen formation in CEACAM1 transfected MCF-7 cells grown in 3D culture, there is an additional requirement for stromal or mesenchymal cells (MSCs) for these cells to form xenografts with glandular structures in an orthotopic site. We demonstrate that optimal in vitro conditions include both Matrigel and MSCs and that the inclusion of collagen I inhibits xenograft differentiation. Additionally, there is no need to remove the nascent murine mammary gland. The previously observed difference in gland development between the long and short cytoplasmic domain isoforms of CEACAM1 is no longer observed in pregnant NOD/SCID mice suggesting that stimulation of the mammary fat pad by pregnancy critically affects xenograft differentiation.

  1. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC

    PubMed Central

    Herz, Corinna; Hertrampf, Anke; Zimmermann, Stefan; Stetter, Nadine; Wagner, Meike; Kleinhans, Claudia; Erlacher, Miriam; Schüler, Julia; Platz, Stefanie; Rohn, Sascha; Mersch-Sundermann, Volker; Lamy, Evelyn

    2014-01-01

    In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level. PMID:25256442

  2. Layered MoS2 Hollow Spheres for Highly-Efficient Photothermal Therapy of Rabbit Liver Orthotopic Transplantation Tumors.

    PubMed

    Tan, Longfei; Wang, Shengping; Xu, Ke; Liu, Tianlong; Liang, Ping; Niu, Meng; Fu, Changhui; Shao, Haibo; Yu, Jie; Ma, Tengchuang; Ren, Xiangling; Li, Hong; Dou, Jianping; Ren, Jun; Meng, Xianwei

    2016-04-01

    Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand-new MoS2 nanostructure is designed and fabricated, i.e., layered MoS2 hollow spheres (LMHSs) with strong absorption in near-infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as-prepared LMHSs exhibit unique electronic properties comparing with MoS2 nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX2 tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor-targeting delivery and cancer theranostic application.

  3. Iron-Oxide-Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model.

    PubMed

    Wang, Kui; Kievit, Forrest M; Sham, Jonathan G; Jeon, Mike; Stephen, Zachary R; Bakthavatsalam, Arvind; Park, James O; Zhang, Miqin

    2016-01-27

    Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Small interfering RNA (siRNA) holds promise as a new class of therapeutics for HCC, as it can achieve sequence-specific gene knockdown with low cytotoxicity. However, the main challenge in the clinical application of siRNA lies in the lack of effective delivery approaches that need to be highly specific and thus incur low or no systemic toxicity. Here, a nonviral nanoparticle-based gene carrier is presented that can specifically deliver siRNA to HCC. The nanovector (NP-siRNA-GPC3 Ab) is made of an iron oxide core coated with chitosan-polyethylene glycol (PEG) grafted polyethyleneimine copolymer, which is further functionalized with siRNA and conjugated with a monoclonal antibody (Ab) against human glypican-3 (GPC3) receptor highly expressed in HCC. A rat RH7777 HCC cell line that coexpresses human GPC3 and firefly luciferase (Luc) is established to evaluate the nanovector. The nanoparticle-mediated delivery of siRNA against Luc effectively suppresses Luc expression in vitro without notable cytotoxicity. Significantly, NP-siLuc-GPC3 Ab administered intravenously in an orthotopic model of HCC is able to specifically bound to tumor and induce remarkable inhibition of Luc expression. The findings demonstrate the potential of using this nanovector for targeted delivery of therapeutic siRNA to HCC.

  4. A“Proteoglycan Targeting Strategy” for the Scintigraphic Imaging and Monitoring of the Swarm Rat Chondrosarcoma Orthotopic Model

    PubMed Central

    Peyrode, Caroline; Gouin, François; Vidal, Aurélien; Auzeloux, Philippe; Besse, Sophie; Dauplat, Marie-Mélanie; Askienazy, Serge; Heymann, Dominique; Chezal, Jean-Michel; Redini, Françoise; Miot-Noirault, Elisabeth

    2011-01-01

    Our lab developed 99mTc-NTP 15-5 radiotracer as targeting proteoglycans (PGs) for the scintigraphic imaging of joint. This paper reports preclinical results of 99mTc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC). 99mTc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume. Tumours were characterized by histology and PG assay. SRC exhibited a significant 99mTc-NTP 15-5 uptake at very early stage after implant (with tumour/muscle ratio of 1.61 ± 0.14), whereas no measurable tumour was evidenced. As tumour grew, mean tumour/muscle ratio was increased by 2.4, between the early and late stage of pathology. Bone scintigraphy failed to image chondrosarcoma, even at the later stage of study. 99mTc-NTP 15-5 imaging provided a suitable set of quantitative criteria for the in vivo characterization of chondrosarcoma behaviour in bone environment, useful for achieving a greater understanding of the pathology. PMID:21331335

  5. Advances in testosterone replacement therapy.

    PubMed

    Gooren, Louis J G

    2009-01-01

    The major goal of androgen substitution is to replace testosterone at levels as close to physiological concentrations as is possible. The mainstay of testosterone susbstitution are parenteral testosterone esters (enanthate and cypionate) to be administered every 2-3 weeks. A major disadvantage is the strongly fluctuating levels of plasma testosterone which are at least 50% of the time not in the physiological range. A significant improvement is parenteral testosterone undecanoate producing normal plasma testosterone for 12 weeks. Subcutaneous testosterone implants provide the patient, depending on the dose of implants, with normal plasma testosterone for 3-6 months. Its use is, however, not widespread. Oral testosterone undecanoate dissolved in oil bypasses the liver via its lymphatic absorption, but resulting plasma levels are erratic. Transdermal testosterone preparations have already been available for two decades. Transdermal testosterone gel produces attractive pharmocokinetic serum testosterone profiles and offers greater flexibility in dosing. Transdermal gel has been recommended in elderly males. In case of complications its use can be discontinued immediately. Oromucosal testosterone preparations are being developed. Testosterone replacement is usually of long duration, and patient compliance is of utmost importance. Therefore, the patient must be involved in the selection of the type of testosterone preparation. PMID:19011287

  6. The future of nicotine replacement.

    PubMed

    Russell, M A

    1991-05-01

    Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether.

  7. Raised replacement heifers: some economic considerations.

    PubMed

    Hughes, Harlan

    2013-11-01

    This article lays out the recommended procedure for determining the economic cost of developing a proposed set of replacement heifers. In particular, a 6-step process that calculates the economic cost of developing a raised pregnant replacement heifer is described.

  8. UHMWPE-based nanocomposite as a material for damaged cartilage replacement.

    PubMed

    Senatov, F S; Kopylov, A N; Anisimova, N Yu; Kiselevsky, M V; Maksimkin, A V

    2015-03-01

    In the present work dispersion-strengthened nanocomposites based on ultra-high molecular weight polyethylene (UHMWPE) after mechanical activation were studied. Mechanical activation was performed for hardening of the boundaries between the polymer particles, reducing the fusion defects and increasing of wear-resistance. Three types of samples were prepared: UHMWPE, UHMWPE/Al2O3 nanocomposite and UHMWPE/Al2O3 nanocomposite after mechanical activation. UHMWPE/Al2O3 nanocomposites prepared with mechanical activation show the best mechanical properties in compression and higher wear-resistance. UHMWPE/Al2O3 nanocomposites prepared with mechanical activation were chosen for in vivo study by orthotopical transplantation in rats. Animals' activity has been being monitored for 60days after surgery. No signs of inflammation, cellular infiltration, destruction of material or bone-cartilage defect were found. Implanted sample has not changed its position of implantation, there were no any shifts. Obtained data shows that UHMWPE-based nanocomposite is a promising material for creating bioimplants for cartilage defect replacement.

  9. Cardiac valve replacement: Experience in 2400 patients

    PubMed Central

    Papo, Isidor; Albreht, Mis̆a; Martinović, Nebojs̆a; Sokolić, Josip; Marenović, Tomislav

    1981-01-01

    In the series described here, 2400 patients over a 15-year period underwent surgery for correction of acquired valvular heart disease. Of these, 1586 patients had single valve replacement, 714 had double valve replacement, and 100 had triple valve replacement. Concomitant surgery for associated congenital and acquired lesions was done in 114 patients. The hospital mortality was 9.16%. PMID:15216220

  10. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means...

  11. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means...

  12. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means...

  13. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means...

  14. Hip Replacement - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Hip Replacement (Arabic) العربية Bilingual PDF Health Information Translations Bosnian (Bosanski) Total Hip Replacement Potpuna zamjena kuka - Bosanski (Bosnian) Bilingual PDF Health Information Translations Chinese - Simplified (简体中文) Total Hip Replacement 全髋关节置换 - 简体中文 ( ...

  15. Knee Replacement - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Knee Replacement (Arabic) العربية Bilingual PDF Health Information Translations Bosnian (Bosanski) Total Knee Replacement Potpuna zamjena koljena - Bosanski (Bosnian) Bilingual PDF Health Information Translations Chinese - Simplified (简体中文) Total Knee Replacement 全膝关节置换 - 简体中文 ( ...

  16. Estrogen Replacement Therapy for Stroke

    PubMed Central

    Pabon, Mibel; Tamboli, Cyrus; Tamboli, Sarosh; Acosta, Sandra; De La Pena, Ike; Sanberg, Paul R.; Tajiri, Naoki; Kaneko, Yuji; Borlongan, Cesar V.

    2014-01-01

    Stroke is the third most common cause of death and severe disability among Western populations. Overall, the incidence of stroke is uniformly higher in men than in women. Stroke is rare in women during the reproductive years and rapidly increases after menopause, strongly suggesting that estrogen (E2) plays an important role in the prevention of stroke. Ongoing studies are currently evaluating both the benefits and the risks associated with E2 replacement therapy and hormone replacement therapy in stroke. Equally important is the role of E2 receptor (ER), as studies indicate that ER populations in several tissue sites may significantly change during stress and aging. Such changes may affect the patient’s susceptibility to neurological disorders including stroke and greatly affect the response to selective E2 receptor modulators (SERMs). Replacement therapies may be inefficient with low ER levels. The goal of this review paper is to discuss an animal model that will allow investigations of the potential therapeutic effects of E2 and its derivatives in stroke. We hypothesize that E2 neuroprotection is, in part, receptor mediated. This hypothesis is a proof-of-principle approach to demonstrate a role for specific ER subtypes in E2 neuroprotection. To accomplish this, we use a retroviral-mediated gene transfer strategy that expresses subtypes of the ER gene in regions of the rat brain most susceptible to neuronal damage, namely, the striatum and the cortex. The animal model is exposed to experimental stroke conditions involving middle cerebral artery occlusion (MCAo) method, and eventually the extent of neuronal damage will be evaluated. A reduction in neuronal damage is expected when E2 is administered with specific ER subtypes. From this animal model, an optimal E2 dose and treatment regimen can be determined. The animal model can help identify potential E2-like therapeutics in stroke and screen for beneficial or toxic additives present in commercial E2

  17. Molecular replacement then and now

    SciTech Connect

    Scapin, Giovanna

    2013-11-01

    A brief overview, with examples, of the evolution of molecular-replacement methods and models over the past few years is presented. The ‘phase problem’ in crystallography results from the inability to directly measure the phases of individual diffracted X-ray waves. While intensities are directly measured during data collection, phases must be obtained by other means. Several phasing methods are available (MIR, SAR, MAD, SAD and MR) and they all rely on the premise that phase information can be obtained if the positions of marker atoms in the unknown crystal structure are known. This paper is dedicated to the most popular phasing method, molecular replacement (MR), and represents a personal overview of the development, use and requirements of the methodology. The first description of noncrystallographic symmetry as a tool for structure determination was explained by Rossmann and Blow [Rossmann & Blow (1962 ▶), Acta Cryst.15, 24–31]. The term ‘molecular replacement’ was introduced as the name of a book in which the early papers were collected and briefly reviewed [Rossmann (1972 ▶), The Molecular Replacement Method. New York: Gordon & Breach]. Several programs have evolved from the original concept to allow faster and more sophisticated searches, including six-dimensional searches and brute-force approaches. While careful selection of the resolution range for the search and the quality of the data will greatly influence the outcome, the correct choice of the search model is probably still the main criterion to guarantee success in solving a structure using MR. Two of the main parameters used to define the ‘best’ search model are sequence identity (25% or more) and structural similarity. Another parameter that may often be undervalued is the quality of the probe: there is clearly a relationship between the quality and the correctness of the chosen probe and its usefulness as a search model. Efforts should be made by all structural biologists to

  18. ORO. The physical developer replacement?

    PubMed

    Wood, Michael A; James, Tim

    2009-12-01

    In the process of fingerprint development Physical Developer has been largely the method of choice on porous surfaces after coming into contact with wet environments. It is only recently that a new technique has been identified which could replace this standard technique. This study aims to build on previous research and expand knowledge regarding the technique. The study built on previous research and compared Physical Developer to Oil Red O, testing both on four paper types, while being placed in three different water types and an accelerant for various amounts of time. Marks were placed with both heavily 'loaded' sebaceous fingers and 'normal' un-washed fingers. Results show that Oil Red O consistently produced clearer more detailed marks from the 'loaded' fingers, but neither technique proved to work better on the 'normal' marks. Neither technique developed any prints from the accelerant.

  19. Optimal randomized scheduling by replacement

    SciTech Connect

    Saias, I.

    1996-05-01

    In the replacement scheduling problem, a system is composed of n processors drawn from a pool of p. The processors can become faulty while in operation and faulty processors never recover. A report is issued whenever a fault occurs. This report states only the existence of a fault but does not indicate its location. Based on this report, the scheduler can reconfigure the system and choose another set of n processors. The system operates satisfactorily as long as, upon report of a fault, the scheduler chooses n non-faulty processors. We provide a randomized protocol maximizing the expected number of faults the system can sustain before the occurrence of a crash. The optimality of the protocol is established by considering a closely related dual optimization problem. The game-theoretic technical difficulties that we solve in this paper are very general and encountered whenever proving the optimality of a randomized algorithm in parallel and distributed computation.

  20. Replacement Sequence of Events Generator

    NASA Technical Reports Server (NTRS)

    Fisher, Forest; Gladden, Daniel Wenkert Roy; Khanampompan, Teerpat

    2008-01-01

    The soeWINDOW program automates the generation of an ITAR (International Traffic in Arms Regulations)-compliant sub-RSOE (Replacement Sequence of Events) by extracting a specified temporal window from an RSOE while maintaining page header information. RSOEs contain a significant amount of information that is not ITAR-compliant, yet that foreign partners need to see for command details to their instrument, as well as the surrounding commands that provide context for validation. soeWINDOW can serve as an example of how command support products can be made ITAR-compliant for future missions. This software is a Perl script intended for use in the mission operations UNIX environment. It is designed for use to support the MRO (Mars Reconnaissance Orbiter) instrument team. The tool also provides automated DOM (Distributed Object Manager) storage into the special ITAR-okay DOM collection, and can be used for creating focused RSOEs for product review by any of the MRO teams.

  1. Mitochondrial Replacement: Ethics and Identity

    PubMed Central

    Wilkinson, Stephen; Appleby, John B.

    2015-01-01

    Abstract Mitochondrial replacement techniques (MRTs) have the potential to allow prospective parents who are at risk of passing on debilitating or even life‐threatening mitochondrial disorders to have healthy children to whom they are genetically related. Ethical concerns have however been raised about these techniques. This article focuses on one aspect of the ethical debate, the question of whether there is any moral difference between the two types of MRT proposed: Pronuclear Transfer (PNT) and Maternal Spindle Transfer (MST). It examines how questions of identity impact on the ethical evaluation of each technique and argues that there is an important difference between the two. PNT, it is argued, is a form of therapy based on embryo modification while MST is, instead, an instance of selective reproduction. The article's main ethical conclusion is that, in some circumstances, there is a stronger obligation to use PNT than MST. PMID:26481204

  2. ORO. The physical developer replacement?

    PubMed

    Wood, Michael A; James, Tim

    2009-12-01

    In the process of fingerprint development Physical Developer has been largely the method of choice on porous surfaces after coming into contact with wet environments. It is only recently that a new technique has been identified which could replace this standard technique. This study aims to build on previous research and expand knowledge regarding the technique. The study built on previous research and compared Physical Developer to Oil Red O, testing both on four paper types, while being placed in three different water types and an accelerant for various amounts of time. Marks were placed with both heavily 'loaded' sebaceous fingers and 'normal' un-washed fingers. Results show that Oil Red O consistently produced clearer more detailed marks from the 'loaded' fingers, but neither technique proved to work better on the 'normal' marks. Neither technique developed any prints from the accelerant. PMID:20120606

  3. Modulation of HCV reinfection after orthotopic liver transplantation by fibroblast growth factor-2 and other non-interferon mediators

    PubMed Central

    Van, Nguyen Dinh; Falk, Christine S; Sandmann, Lisa; Vondran, Florian W R; Helfritz, Fabian; Wedemeyer, Heiner; Manns, Michael P; Ciesek, Sandra; von Hahn, Thomas

    2016-01-01

    Objective In HCV infected individuals graft infection occurs shortly after orthotopic liver transplantation (OLT). We aimed to describe the composition of the inflammatory response at this time, how it affects the HCV replication cycle and identify novel proviral and antiviral factors. Design We used a Luminex assay to quantify 50 inflammatory mediators in sera before and shortly after OLT. In vitro grown HCV based on the JFH-1 isolate were used to characterise the effects of patient sera and individual mediators on HCV. Results Although the mediator composition is highly variable between individuals, sera drawn immediately post-OLT significantly enhance HCV infectivity compared with control sera from before OLT in about half of the cases. Among 27 non-interferon inflammatory mediators fibroblast growth factor (FGF)-2 stood out as it enhanced HCV RNA replication and release of infectious particles. The effect was concentration-dependent and detectable in dividing and non-dividing cells. Moreover, pharmacological inhibition of FGF-2 receptor signalling abrogated the enhancing effect of FGF-2 and inhibited HCV replication in the absence of serum FGF-2 suggesting that HCV replication is dependent on basal activation of the FGF-2 triggered signalling pathway. Finally, in individuals with chronic HCV infection with high viral load, serum FGF-2 was significantly higher compared with those with low viral load. Conclusions Although no single mediator may account for this effect, serum shortly post-OLT enhances HCV infection. FGF-2 is a novel endogenous driver of HCV replication and a potential therapeutic target. PMID:25800783

  4. Monitoring Oxygen Levels in Orthotopic Human Glioma Xenograft Following Carbogen Inhalation and Chemotherapy by Implantable Resonator Based Oximetry

    PubMed Central

    Hou, Huagang; Nemani, Venkata Krishnamurthy; Du, Gaixin; Montano, Ryan; Song, Rui; Gimi, Barjor; Swartz, Harold M.; Eastman, Alan; Khan, Nadeem

    2014-01-01

    Hypoxia is a critical hallmark of glioma, and significantly compromises treatment efficacy. Unfortunately, techniques for monitoring glioma pO2 to facilitate translational research are lacking. Furthermore, poor prognoses of patients with malignant glioma, in particular glioblastoma multiforme, warrant effective strategies that can inhibit hypoxia and improve treatment outcome. EPR oximetry using implantable resonators was implemented for monitoring pO2 in normal cerebral tissue and U251 glioma in mice. Breathing carbogen (95% O2 + 5% CO2) was tested for hyperoxia in the normal brain and glioma xenografts. A new strategy to inhibit glioma growth by rationally combining gemcitabine and MK-8776, a cell cycle checkpoint inhibitor, was also investigated. The mean pO2 of left and right hemisphere were approximately 56 – 69 mmHg in the normal cerebral tissue of mice. The mean baseline pO2 of U251 glioma on the first and fifth day of measurement was 21.9 ± 3.7 and 14.1 ± 2.4 mmHg, respectively. The mean brain pO2 including glioma increased by at least 100% on carbogen inhalation, although the response varied between the animals over days. Treatment with gemcitabine + MK-8776 significantly increased pO2 and inhibited glioma growth assessed by MRI. In conclusion, EPR oximetry with implantable resonators can be used to monitor the efficacy of carbogen inhalation and chemotherapy on orthotopic glioma in mice. The increase in glioma pO2 of mice breathing carbogen can be used to improve treatment outcome. The treatment with gemcitabine + MK-8776 is a promising strategy that warrants further investigation. PMID:25111969

  5. Surgery combined with controlled-release doxorubicin silk films as a treatment strategy in an orthotopic neuroblastoma mouse model

    PubMed Central

    Chiu, B; Coburn, J; Pilichowska, M; Holcroft, C; Seib, F P; Charest, A; Kaplan, D L

    2014-01-01

    Background: Neuroblastoma tumour resection goal is maximal tumour removal. We hypothesise that combining surgery with sustained, local doxorubicin application can control tumour growth. Methods: We injected human neuroblastoma cells into immunocompromised mouse adrenal gland. When KELLY cell-induced tumour volume was >300 mm3, 80–90% of tumour was resected and treated as follows: instantaneous-release silk film with 100 μg doxorubicin (100IR), controlled-release film with 200 μg (200CR) over residual tumour bed; and 100 and 200 μg intravenous doxorubicin (100IV and 200IV). Tumour volume was measured and histology analysed. Results: Orthotopic tumours formed with KELLY, SK-N-AS, IMR-32, SH-SY5Y cells. Tumours reached 1800±180 mm3 after 28 days, 2200±290 mm3 after 35 days, 1280±260 mm3 after 63 days, and 1700±360 mm3 after 84 days, respectively. At 3 days post KELLY tumour resection, tumour volumes were similar across all groups (P=0.6210). Tumour growth rate was similar in untreated vs control film, 100IV vs 100IR, and 100IV vs 200IV. There was significant difference in 100IR vs 200CR (P=0.0004) and 200IV vs 200CR (P=0.0003). Tumour growth with all doxorubicin groups was slower than that of control (P: <0.0001–0.0069). At the interface of the 200CR film and tumour, there was cellular necrosis, surrounded by apoptotic cells before reaching viable tumour cells. Conclusions: Combining surgical resection and sustained local doxorubicin treatment is effective in tumour control. Administering doxorubicin in a local, controlled manner is superior to giving an equivalent intravenous dose in tumour control. PMID:24921912

  6. 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.

  7. Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

    PubMed Central

    Coutinho de Souza, Patricia; Mallory, Samantha; Smith, Nataliya; Saunders, Debra; Li, Xiao-Nan; McNall-Knapp, Rene Y.; Fung, Kar-Ming; Towner, Rheal A.

    2015-01-01

    Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients. PMID:26248280

  8. Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.

    PubMed

    Poczobutt, Joanna M; De, Subhajyoti; Yadav, Vinod K; Nguyen, Teresa T; Li, Howard; Sippel, Trisha R; Weiser-Evans, Mary C M; Nemenoff, Raphael A

    2016-03-15

    Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and they alter their phenotype in response to local environmental cues. Whereas the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes has not been well studied, particularly in lung cancer. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multimarker flow cytometry, we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and expresses multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor and selectively expresses a panel of chemokine genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict outcomes in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and they suggest that distinct populations play specific roles in tumor progression. PMID:26873985

  9. Pulsed Versus Conventional Radiation Therapy in Combination With Temozolomide in a Murine Orthotopic Model of Glioblastoma Multiforme

    SciTech Connect

    Lee, David Y.; Chunta, John L.; Park, Sean S.; Huang, Jiayi; Martinez, Alvaro A.; Grills, Inga S.; Krueger, Sarah A.; Wilson, George D.; Marples, Brian

    2013-08-01

    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 a 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.

  10. Dental ontogeny and replacement in Pliosauridae.

    PubMed

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-11-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or 'movement paths', of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context. PMID:26715998

  11. Dental ontogeny and replacement in Pliosauridae.

    PubMed

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-11-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or 'movement paths', of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context.

  12. Dental ontogeny and replacement in Pliosauridae

    PubMed Central

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-01-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or ‘movement paths’, of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context. PMID:26715998

  13. The Value of SPECT/CT in Monitoring Prefabricated Tissue-Engineered Bone and Orthotopic rhBMP-2 Implants for Mandibular Reconstruction

    PubMed Central

    Zhou, Miao; Peng, Xin; Mao, Chi; Tian, Jia-he; Zhang, Shu-wen; Xu, Fang; Tu, Jing-jing; Liu, Sheng; Hu, Min; Yu, Guang-yan

    2015-01-01

    Bone tissue engineering shows good prospects for mandibular reconstruction. In recent studies, prefabricated tissue-engineered bone (PTEB) by recombinant human bone morphogenetic proteins (rhBMPs) applied in vivo has found to be an effective alternative for autologous bone grafts. However, the optimal time to transfer PTEB for mandibular reconstruction is still not elucidated. Thus, here in an animal experiment of rhesus monkey, the suitable transferring time for PTEB to reconstruct mandibular defects was evaluated by 99mTc-MDP SPECT/CT, and its value in monitoring orthotopic rhBMP-2 implants for mandibular reconstruction was also evaluated. The result of SPECT/CT showed higher 99mTc-MDP uptake, indicating osteoinductivity, in rhBMP-2 incorporated demineralized freeze-dried bone allograft (DFDBA) and coralline hydroxyapatite (CHA) implants than those without BMP stimulation. 99mTc-MDP uptake of rhBMP-2 implant peaked at 8 weeks following implantation while CT showed the density of these implants increased after 13 weeks’ prefabrication. Histology confirmed that mandibular defects were repaired successfully with PTEB or orthotopically rhBMP-2 incorporated CHA implants, in accordance with SPECT/CT findings. Collectively, data shows 99mTc-MDP SPECT/CT is a sensitive and noninvasive tool to monitor osteoinductivity and bone regeneration of PTEB and orthotopic implants. The PTEB achieved peak osteoinductivity and bone density at 8 to 13 weeks following ectopic implantation, which would serve as a recommendable time frame for its transfer to mandibular reconstruction. PMID:26340447

  14. Atelocollagen-mediated intravenous siRNA delivery specific to tumor tissues orthotopically xenografted in prostates of nude mice and its anticancer effects.

    PubMed

    Yuan, Yuan; Makita, Naoki; Cao, Dongliang; Mihara, Keichiro; Kadomatsu, Kenji; Takei, Yoshifumi

    2015-04-01

    Successful short interfering RNA (siRNA)-based therapy for cancers depends on functional siRNA delivery specific to tumors. In our previous report, we have shown systemic siRNA delivery specific to human prostate cancer cell line PC-3 subcutaneous tumors in nude mice by atelocollagen, a collagen derivative, for formulating a complex with siRNA. We used an siRNA for human Bcl-xL as a model target. In the present study, we examined the antitumor effect on PC-3 orthotopic tumors in nude mice, as these tumors resemble the human clinical situation. The systemic intravenous administration of the complex (siRNA, 50 μg/shot) significantly reduced Bcl-xL expression and induced apoptosis in the tumors, and suppressed their growth. Liver metastasis was also inhibited in the orthotopic model. We successfully showed tumor-specific accumulation of the siRNA by Cy3-labeled siRNA and the direct quantification of the siRNA via reverse-phase high-performance liquid chromatography. The tumor-specific delivery was achieved by the enhanced permeability and retention effect, which is characteristic of macromolecular drugs. The high expression of vascular endothelial growth factor-A in the tumors provided adequate conditions to promote the permeability in the tumors, and to finally form the enhanced permeability and retention effect. In conclusion, our siRNA delivery is specific to the PC-3 orthotopic tumors in nude mice, and is practically feasible to treat tumors.

  15. Boswellic Acid Suppresses Growth and Metastasis of Human Pancreatic Tumors in an Orthotopic Nude Mouse Model through Modulation of Multiple Targets

    PubMed Central

    Park, Byoungduck; Prasad, Sahdeo; Yadav, Vivek; Sung, Bokyung; Aggarwal, Bharat B.

    2011-01-01

    Pancreatic cancer (PaCa) is one of the most lethal cancers, with an estimated 5-year survival of <5% even when patients are given the best treatment available. In addition, these treatments are often toxic and expensive, thus new agents which are safe, affordable and effective are urgently needed. We describe here the results of our study with acetyl-11-keto-β-boswellic acid (AKBA), an agent obtained from an Ayurvedic medicine, gum resin of Boswellia serrata. Whether AKBA has an activity against human PaCa, was examined in in vitro models and in an orthotopic nude mouse model of PaCa. We found that AKBA inhibited the proliferation of four different PaCa cell lines (AsPC-1, PANC-28, and MIA PaCa-2 with K-Ras and p53 mutations, and BxPC-3 with wild-type K-Ras and p53 mutation). These effects correlated with an inhibition of constitutively active NF-κB and suppression of NF-κB regulating gene expression. AKBA also induced apoptosis, and sensitized the cells to apoptotic effects of gemcitabine. In the orthotopic nude mouse model of PaCa, p.o. administration of AKBA alone (100 mg/kg) significantly inhibited the tumor growth; this activity was enhanced by gemcitabine. In addition, AKBA inhibited the metastasis of the PaCa to spleen, liver, and lungs. This correlated with decreases in Ki-67, a biomarker of proliferation, and CD31, a biomarker of microvessel density, in the tumor tissue. AKBA produced significant decreases in the expression of NF-κB regulating genes in the tissues. Immunohistochemical analysis also showed AKBA downregulated the expression of COX-2, MMP-9, CXCR4, and VEGF in the tissues. Overall these results demonstrate that AKBA can suppress the growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model that correlates with modulation of multiple targets. PMID:22066019

  16. Visual Image Sensor Organ Replacement

    NASA Technical Reports Server (NTRS)

    Maluf, David A.

    2014-01-01

    This innovation is a system that augments human vision through a technique called "Sensing Super-position" using a Visual Instrument Sensory Organ Replacement (VISOR) device. The VISOR device translates visual and other sensors (i.e., thermal) into sounds to enable very difficult sensing tasks. Three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. Because the human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns, the translation of images into sounds reduces the risk of accidentally filtering out important clues. The VISOR device was developed to augment the current state-of-the-art head-mounted (helmet) display systems. It provides the ability to sense beyond the human visible light range, to increase human sensing resolution, to use wider angle visual perception, and to improve the ability to sense distances. It also allows compensation for movement by the human or changes in the scene being viewed.

  17. Delivery of testosterone replacement therapy.

    PubMed

    Hameed, Asjad; Brothwood, Theresa; Bouloux, Pierre

    2003-10-01

    Optimal testosterone replacement therapy remains a considerable challenge for the estimated five out of 1000 men in the general community with androgen deficiency. Oral delivery is not possible due to rapid first pass metabolism and short half-life. Testosterone derivatives have been developed to enhance intrinsic androgenic potency, prolong duration of action, or improve oral bioavailability of synthetic androgens. Structural modification of testosterone include 17 beta-esterification, 17 alpha-alkylation, 1-methylation, addition of a 19-normethyl group, and 7 alpha-methylation. Currently, oral (testosterone undecanoate), transcutaneous (Andropatch, Virormone, Testoderm (ALZA Corp), Testogel), sublingual (testosterone cyclodextrin), intramuscular (Sustanon, Primoteston Depot), and fused crystalline testosterone pellet preparations are available for clinical use. Transbuccal testosterone systems have also been developed for clinical use and require twice daily application. Suspensions of biodegradable microspheres consisting of a polyglycolide-lactide matrix laden with testosterone can deliver stable, physiological levels of testosterone for 2 to 3 months. Micronized testosterone has low oral bioavailability requiring high daily doses. 7 alpha-Methyl 19-nortestosterone, a potent, synthetic androgen free of hepatotoxicity, has tissue-specific selectivity, being susceptible to aromatization but not 5 alpha-reduction, thereby potentially avoiding intraprostatic androgen amplification. PMID:14649214

  18. Autologous tracheal replacement for cancer.

    PubMed

    Fabre, Dominique; Fadel, Elie; Mussot, Sacha; Kolb, Frederic; Leymarie, Nicolas; Mercier, Olaf; Le Chevalier, Thierry; Dartevelle, Philippe G

    2015-12-01

    Surgical research has failed during fifty years to find an ideal substitute for the trachea after extended resection. All the prostheses could erode the adjacent structures or lead to infection or obstructive issues. Innovation in surgery development has been improved using novel techniques of plastic surgery. During the last ten years, we have developed a technique using free fasciocutaneous flaps. This allows us to construct tubes for tracheal replacement. The most accurate flap used for this technique is the forearm free flap (FFF). Reinforcement of the flap with autologous strips of cartilage harvested from the last ribs offers sufficient resistance to respiratory pressure. This technique is also completely autologous without any stent in the tracheal lumen. From 2004 to 2015 we have already reconstructed the trachea of 16 patients for 12 primary tracheal neoplasms [including 9 adenoid cystic carcinoma (ACC) and 3 squamous cell carcinoma (SCC)], 3 secondary tracheal Neoplasms and one for benign lesion. This article describes the indications, determination of resectability, patient selection, subheading for surgery, postoperative management and results of this technique. PMID:26730758

  19. 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

    2016-04-01

    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

  20. Clinical Lessons to Be Learned from Patients Developing Chronic Myeloid Leukemia While on Immunosuppressive Therapy after Solid Organ Transplantation: Yet Another Case after Orthotopic Heart Transplantation

    PubMed Central

    Oberender, Christian; Kleeberg, Lorenz; Nienhues, Nicola; Dörken, Bernd; Riess, Hanno

    2014-01-01

    Chronic myeloid leukemia developing after transplantation of solid organs and concomitant immunosuppression is a rare but still significant clinical phenomenon. We here describe an additional case of a 62-year-old male patient developing CML after orthotopic heart transplantation and medication with cyclosporine A, mofetil-mycophenolate, and steroids. Initial antileukemic therapy was imatinib at a standard dose and within 15 months of therapy a complete cytogenetic response was noted. In this report we discuss the clinical implications of these rare but biologically important cases. PMID:25478254

  1. Efficacy of Tumor-Targeting Salmonella A1-R on a Melanoma Patient-Derived Orthotopic Xenograft (PDOX) Nude-Mouse Model

    PubMed Central

    Yamamoto, Mako; Zhao, Ming; Hiroshima, Yukihiko; Zhang, Yong; Shurell, Elizabeth; Eilber, Fritz C.; Bouvet, Michael; Noda, Makoto; Hoffman, Robert M.

    2016-01-01

    Tumor-targeting Salmonella enterica serovar Typhimurium A1-R (Salmonella A1-R) had strong efficacy on a melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse model. GFP-expressing Salmonella A1-R highly and selectively colonized the PDOX melanoma and significantly suppressed tumor growth (p = 0.021). The combination of Salmonella A1-R and cisplatinum (CDDP), both at low-dose, also significantly suppressed the growth of the melanoma PDOX (P = 0.001). Salmonella A1-R has future clinical potential for combination chemotherapy with CDDP of melanoma, a highly-recalcitrant cancer. PMID:27500926

  2. Biology of tooth replacement in amniotes

    PubMed Central

    Whitlock, John A; Richman, Joy M

    2013-01-01

    Tooth replacement is a common trait to most vertebrates, including mammals. Mammals, however, have lost the capacity for continuous tooth renewal seen in most other vertebrates, and typically have only 1–2 generations of teeth. Here, we review the mechanisms of tooth replacement in reptiles and mammals, and discuss in detail the current and historical theories on control of timing and pattern of tooth replacement and development. PMID:23788284

  3. Microcrystalline cellulose replacement in cakes and biscuits.

    PubMed

    Brys, K D; Zabik, M E

    1976-07-01

    Sensory and physical characteristics of cakes and biscuits with up to 60 per cent of flour replaced, volume for volume, with microcrystalline cellulose were compared with those of the respective controls. High quality products were obtained at replacement levels of 40 and 20 per cent, respectively, in lean-formula cakes and in biscuits. At these replacement levels, caloric density was reduced by 12 and 10 per cent, respectively, in the cakes and biscuits.

  4. Total joint replacement preadmission programs.

    PubMed

    Messer, B

    1998-01-01

    Patients begin to formulate their expectations of the postoperative hospitalization during the preadmission program. The challenge is to better understand the factors patients consider when formulating judgments about the quality of preadmission education. For example, it may be that perceptions of the preadmission program are influenced by what patients believe about their postoperative pain and functional abilities. Specific attention needs to be given both preoperatively and postoperatively to instructing patients on realistic expectations for recovery. One other method of measuring patient outcomes is with the Health Status Profile (SF-36) (Response Healthcare Information Management, 1995). The SF-36 approach emphasizes the outcome of medical care as the patient sees it, in addition to a clinical evaluation of successful health care. This form is currently initiated in the physician's office and returned for scanning at the preadmission class. The patient then completes another SF-36 at 6 months and every year thereafter to compare measurable outcomes. Patients intending to have elective total joint replacements experience anxiety and require much support and education. An effective preadmission program is a major investment in a patient's recovery, as well as a unique marketing tool to customers. Preadmission programs can be viewed as an opportunity to enhance customer satisfaction. Preadmission clinics are an excellent means for nurses to improve the quality of patient care through patient education. the overall goal of preadmission testing programs is to ensure patient preparedness while increasing quality health care and overall customer satisfaction. To enhance program effectiveness, health care providers must lead collaborative efforts to improve the efficiency of systems. PMID:9601410

  5. Total joint replacement preadmission programs.

    PubMed

    Messer, B

    1998-01-01

    Patients begin to formulate their expectations of the postoperative hospitalization during the preadmission program. The challenge is to better understand the factors patients consider when formulating judgments about the quality of preadmission education. For example, it may be that perceptions of the preadmission program are influenced by what patients believe about their postoperative pain and functional abilities. Specific attention needs to be given both preoperatively and postoperatively to instructing patients on realistic expectations for recovery. One other method of measuring patient outcomes is with the Health Status Profile (SF-36) (Response Healthcare Information Management, 1995). The SF-36 approach emphasizes the outcome of medical care as the patient sees it, in addition to a clinical evaluation of successful health care. This form is currently initiated in the physician's office and returned for scanning at the preadmission class. The patient then completes another SF-36 at 6 months and every year thereafter to compare measurable outcomes. Patients intending to have elective total joint replacements experience anxiety and require much support and education. An effective preadmission program is a major investment in a patient's recovery, as well as a unique marketing tool to customers. Preadmission programs can be viewed as an opportunity to enhance customer satisfaction. Preadmission clinics are an excellent means for nurses to improve the quality of patient care through patient education. the overall goal of preadmission testing programs is to ensure patient preparedness while increasing quality health care and overall customer satisfaction. To enhance program effectiveness, health care providers must lead collaborative efforts to improve the efficiency of systems.

  6. Reoperations Following Cervical Disc Replacement.

    PubMed

    Skovrlj, Branko; Lee, Dong-Ho; Caridi, John Michael; Cho, Samuel Kang-Wook

    2015-06-01

    Cervical disc replacement (CDR) has emerged as an alternative surgical option to cervical arthrodesis. With increasing numbers of patients and longer follow-ups, complications related to the device and/or aging spine are growing, leaving us with a new challenge in the management and surgical revision of CDR. The purpose of this study is to review the current literature regarding reoperations following CDR and to discuss about the approaches and solutions for the current and future potential complications associated with CDR. The published rates of reoperation (mean, 1.0%; range, 0%-3.1%), revision (mean, 0.2%; range, 0%-0.5%), and removal (mean, 1.2%; range, 0%-1.9%) following CDR are low and comparable to the published rates of reoperation (mean, 1.7%; range; 0%-3.4%), revision (mean, 1.5%; range, 0%-4.7%), and removal (mean, 2.0%; range, 0%-3.4%) following cervical arthrodesis. The surgical interventions following CDR range from the repositioning to explantation followed by fusion or the reimplantation to posterior foraminotomy or fusion. Strict patient selection, careful preoperative radiographic review and surgical planning, as well as surgical technique may reduce adverse events and the need for future intervention. Minimal literature and no guidelines exist for the approaches and techniques in revision and for the removal of implants following CDR. Adherence to strict indications and precise surgical technique may reduce the number of reoperations, revisions, and removals following CDR. Long-term follow-up studies are needed, assessing the implant survivorship and its effect on the revision and removal rates. PMID:26097667

  7. The unstable total hip replacement

    PubMed Central

    D'Angelo, F; Murena, L; Zatti, G; Cherubino, P

    2008-01-01

    Background: Dislocation is one of the most common complications of total hip arthroplasty with a reported dislocation rate of 3.2%. Despite increased experience with hip replacement, the overall rate has not yet changed. The aim of this paper is to review the most recent literature published on this topic and indexed in Medline, in order to clarify the main risk factors, and to standardize a treatment protocol of such an important complication of prosthetic surgery. Materials and Methods: Medline database was searched using key words: “hip dislocation”, “hip instability” from 1980-2007. Studies were eligible for review and included if they met the following criteria: (1) publication in English, (2) clinical trials (3) review papers. Results: The risk of first-time dislocation as a function of time after the surgery is not well understood. Most, but not all, series have demonstrated that the risk of dislocation is highest during the first few months after hip arthroplasty; however, first-time late dislocation can also occur many years after the procedure. Several risk factors were described, including the surgical approach, the diameter of the head, impingement, component malposition, insufficient abductor musculature. In addition, there are also many treatment options, such as long-term bracing after closed reduction, component reorientation, capsulorraphy, trochanteric advancement, increasing offset, exchange of the modular head and the polyethylene liner, insertion of constrained liner. Conclusion: Preventing hip dislocation is obviously the best strategy. Surgeons must take into account patient and surgical risk factors. For patients at high risk for dislocation the surgeon should accurately restore leg length and femoral offset; the use of larger femoral heads, posterior transosseous repair of the capsulotendinous envelope if posterior approach is chosen or the use of a lateral approach should be considered. Proper patient education and postoperative

  8. Peach bottom recirculation piping replacement ALARA program

    SciTech Connect

    Englesson, G.A.; Hilsmeier, A.E.; Mann, B.J.

    1986-01-01

    In late 1983, Philadelphia Electric Company (PECo) began detailed planning to replace the recirculation, residual heat removal, and part of the reactor water cleanup piping of the Peach Bottom Unit 2 reactor. Included in this work was an estimate of the collective exposure expected during piping replacement. That initial estimate, 1945 man-rem, is compared with the actual collective dose incurred during the piping replacement program. Also included are the exposures incurred during two additional tasks (safe end replacement and recirculation pump disassembly and decontamination) not considered in the initial estimate.

  9. Opportunistic replacement of fusion power system parts

    SciTech Connect

    Day, J.A.; George, L.L.

    1981-10-26

    This paper describes a maintenance problem in a fusion power plant. The problem is to specify which life limited parts should be replaced when there is an opportunity. The objective is to minimize the cost rate of replacement parts and of maintenance actions while satisfying a power plant availability constraint. The maintenance policy is to look ahead and replace all parts that will reach their life limits within a time called a screen. Longer screens yield greater system availabilities because more parts are replaced prior to their life limits.

  10. 2'-(2-bromohexadecanoyl)-paclitaxel conjugate nanoparticles for the treatment of non-small cell lung cancer in an orthotopic xenograft mouse model.

    PubMed

    Peng, Lei; Schorzman, Allison N; Ma, Ping; Madden, Andrew J; Zamboni, William C; Benhabbour, Soumya Rahima; Mumper, Russell J

    2014-01-01

    A nanoparticle (NP) formulation with 2'-(2-bromohexadecanoyl)-paclitaxel (Br-16-PX) conjugate was developed in these studies for the treatment of non-small cell lung cancer (NSCLC). The lipophilic paclitaxel conjugate Br-C16-PX was synthesized and incorporated into lipid NPs where the 16-carbon chain enhanced drug entrapment in the drug delivery system and improved in vivo pharmacokinetics. The electron-withdrawing bromine group was used to facilitate the conversion of Br-C16-PX to paclitaxel at the tumor site. The developed system was evaluated in luciferase-expressing A549 cells in vitro and in an orthotopic NSCLC mouse model. The results demonstrated that the Br-C16-PX NPs had a higher maximum tolerated dose (75 mg/kg) than Taxol (19 mg/kg) and provided significantly longer median survival (88 days versus 70 days, P<0.05) in the orthotopic NSCLC model. An improved pharmacokinetic profile was observed for the Br-C16-PX NPs at 75 mg/kg compared to Taxol at 19 mg/kg. The area under the concentration versus time curve (AUC)₀₋₉₆ h of Br-C16-PX from the NPs was 91.7-fold and 49.6-fold greater than Taxol in plasma and tumor-bearing lungs, respectively, which provided sustained drug exposure and higher antitumor efficacy in the NP-treated group.

  11. Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model

    PubMed Central

    Murakami, Takashi; DeLong, Jonathan; Eilber, Fritz C.; Zhao, Ming; Zhang, Yong; Zhang, Nan; Singh, Arun; Russell, Tara; Deng, Samantha; Reynoso, Jose; Quan, Cuong; Hiroshima, Yukihiko; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Chawla, Sant; Endo, Itaru; Hoffman, Robert M.

    2016-01-01

    A patient with high grade undifferentiated pleomorphic soft-tissue sarcoma from a striated muscle was grown orthotopically in the right biceps femoris muscle of mice to establish a patient-derived orthotopic xenograft (PDOX) model. Twenty PDOX mice were divided into 4 groups: G1, control without treatment; G2, Salmonella typhimurium (S. typhimurium)A1-R administered by intratumoral (i.t.) injection once a week for 4 weeks; G3, doxorubicin (DOX) administered by intraperitoneal (i.p.) injection once a week for 4 weeks; G4, S. typhimurium A1-R (i.t.) administered once a week for 2 weeks followed by i.p. doxorubicin once a week for 2 weeks. On day 25 from the initiation of treatment, tumor volume in G2, G3, and G4 was significantly lower than G1. Mice found without gross tumor included one mouse (20%) in G2; one mouse (20%) in G3; and 3 mice (60%) in G4. Body weight loss did not significantly differ between the 3 treated groups or from the untreated control. Histological examination revealed eradication of tumor only in G4 where mice were treated with S. typhimurium A1-R followed by DOX. Our present study indicates future clinical potential of combining S. typhimurium A1-R with chemotherapy such as DOX for soft tissue sarcoma patients. PMID:26859573

  12. Gut Bacteria Drive Kupffer Cell Expansion via MAMP-Mediated ICAM-1 Induction on Sinusoidal Endothelium and Influence Preservation-Reperfusion Injury after Orthotopic Liver Transplantation

    PubMed Central

    Corbitt, Natasha; Kimura, Shoko; Isse, Kumiko; Specht, Susan; Chedwick, Lisa; Rosborough, Brian R.; Lunz, John G.; Murase, Noriko; Yokota, Shinichiro; Demetris, Anthony J.

    2014-01-01

    Bacteria in the gut microbiome shed microbial-associated molecule patterns (MAMPs) into the portal venous circulation, where they augment various aspects of systemic immunity via low-level stimulation. Because the liver is immediately downstream of the intestines, we proposed that gut-derived MAMPs shape liver immunity and affect Kupffer cell (KC) phenotype. Germ-free (GF), antibiotic-treated (AVMN), and conventional (CL) mice were used to study KC development, function, and response to the significant stress of cold storage, reperfusion, and orthotopic transplantation. We found that a cocktail of physiologically active MAMPs translocate into the portal circulation, with flagellin (Toll-like receptor 5 ligand) being the most plentiful and capable of promoting hepatic monocyte influx in GF mice. In MAMP-deficient GF or AVMN livers, KCs are lower in numbers, have higher phagocytic activity, and have lower major histocompatibility complex II expression. MAMP-containing CL livers harbor significantly increased KC numbers via induction of intercellular adhesion molecule 1 on liver sinusoidal endothelium. These CL KCs have a primed yet expected phenotype, with increased major histocompatibility complex class II and lower phagocytic activity that increases susceptibility to liver preservation/reperfusion injury after orthotopic transplantation. The KC number, functional activity, and maturational status are directly related to the concentration of gut-derived MAMPs and can be significantly reduced by broad-spectrum antibiotics, thereby affecting susceptibility to injury. PMID:23159949

  13. Oncolytic virotherapy with an armed vaccinia virus in an orthotopic model of renal carcinoma is associated with modification of the tumor microenvironment

    PubMed Central

    Fend, Laetitia; Remy-Ziller, Christelle; Foloppe, Johann; Kempf, Juliette; Cochin, Sandrine; Barraud, Luc; Accart, Nathalie; Erbs, Philippe; Fournel, Sylvie; Préville, Xavier

    2016-01-01

    ABSTRACT Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted for thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. We evaluated this construct (VV-FCU1) in the orthotopic model of renal carcinoma (RenCa). Systemic administration of VV-FCU1 resulted in orthotopic tumor growth inhibition, despite temporary expression of viral proteins. VV-FCU1 treatment was associated with an infiltration of tumors by CD8+ T lymphocytes and a decrease in the proportion of infiltrating Tregs, thus modifying the ratio of CD8+/CD4+ Treg in favor of CD8+cytotoxic T cells. We demonstrated that VV-FCU1 treatment prolonged survival of animals implanted with RenCa cells in kidney. Depletion of CD8+ T cells abolished the therapeutic effect of VV-FCU1 while depletion of CD4+ T cells enhanced its protective activity. Administration of the prodrug 5-fluorocytosine (5-FC) resulted in a sustained control of tumor growth but did not extend survival. This study shows the importance of CD4+ and CD8+ T cells in vaccinia virus-mediated oncolytic virotherapy and suggests that this approach may be evaluated for the treatment of human renal cell carcinoma. PMID:27057460

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

    SciTech Connect

    Wang Changming; Li Xuan; Song Shibing; Lv Xianjun; Luan Jingyuan; Dong Guoxiang

    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 success 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.

  15. Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model

    PubMed Central

    Mullins, Stefanie; Sulikowski, Michal G.; Martin, Philip; Brown, Lee; Lewis, Arthur; Davies, Gareth; Morrow, Michelle; Wilkinson, Robert W.

    2016-01-01

    Despite the availability of recently developed chemotherapy regimens, survival times for pancreatic cancer patients remain poor. These patients also respond poorly to immune checkpoint blockade therapies (anti-CTLA-4, anti-PD-L1, anti-PD-1), which suggests the presence of additional immunosuppressive mechanisms in the pancreatic tumour microenvironment (TME). CD40 agonist antibodies (αCD40) promote antigen presenting cell (APC) maturation and enhance macrophage tumouricidal activity, and may therefore alter the pancreatic TME to increase sensitivity to immune checkpoint blockade. Here, we test whether αCD40 transforms the TME in a mouse syngeneic orthotopic model of pancreatic cancer, to increase sensitivity to PD-L1 blockade. We found that whilst mice bearing orthotopic Pan02 tumours responded poorly to PD-L1 blockade, αCD40 improved overall survival. αCD40 transformed the TME, upregulating Th1 chemokines, increasing cytotoxic T cell infiltration and promoting formation of an immune cell-rich capsule separating the tumour from the normal pancreas. Furthermore, αCD40 drove systemic APC maturation, memory T cell expansion, and upregulated tumour and systemic PD-L1 expression. Combining αCD40 with PD-L1 blockade enhanced anti-tumour immunity and improved overall survival versus either monotherapy. These data provide further support for the potential of combining αCD40 with immune checkpoint blockade to promote anti-tumour immunity in pancreatic cancer. PMID:26918344

  16. Advantages of a dual-color fluorescence-tracing glioma orthotopic implantation model: Detecting tumor location, angiogenesis, cellular fusion and the tumor microenvironment

    PubMed Central

    SHEN, YUNTIAN; ZHANG, QUANBIN; ZHANG, JINSHI; LU, ZHAOHUI; WANG, AIDONG; FEI, XIFENG; DAI, XINGLIANG; WU, JINDING; WANG, ZHIMIN; ZHAO, YAODONG; TIAN, YE; DONG, JUN; LAN, QING; HUANG, QIANG

    2015-01-01

    Various organs of the body have distinct microenvironments with diverse biological characteristics that can influence the growth of tumors within them. However, the mechanisms underlying the interactions between tumor and host cells are currently not well understood. In the present study, a dual-color fluorescence-tracing glioma orthotopic implantation model was developed, in which C6 rat glioma cells labeled with the red fluorescent dye CM-Dil, and SU3 human glioma cells stably expressing red fluorescence protein, were inoculated into the right caudate nucleus of transgenic female C57BL/6 nude mice expressing enhanced green fluorescent protein. The dual-color tracing with whole-body in vivo fluorescence imaging of xenografts was performed using a live imaging system. Frozen sections of the transplanted tumor were prepared for histological analyses, in order to detect the presence of invading tumor cells, blood vessels and cellular fusion. Dual-color images were able to distinguish between red tumor cells and green host cells. The results of the present study suggested that a dual-color fluorescence-tracing glioma orthotopic implantation model may be convenient for detecting tumor location, angiogenesis, cellular fusion, and the tumor microenvironment. PMID:26668594

  17. Targeting the insulin growth factor-1 receptor with fluorescent antibodies enables high resolution imaging of human pancreatic cancer in orthotopic mouse models

    PubMed Central

    Park, Jeong Youp; Lee, Jin Young; Zhang, Yong; Hoffman, Robert M.; Bouvet, Michael

    2016-01-01

    The goal of the present study was to determine whether insulin-like growth factor-1 receptor (IGF-1R) antibodies, conjugated with bright fluorophores, could enable visualization of pancreatic cancer in orthotopic nude mouse models. IGF-1R antibody (clone 24-31) was conjugated with 550 nm or 650 nm fluorophores. Western blotting confirmed the expression of IGF-1R in Panc-1, BxPC3, and MIAPaCa-2 human pancreatic cancer cell lines. Labeling with fluorophore-conjugated IGF-1R antibody demonstrated fluorescent foci on the membrane of the pancreatic cancer cells. Subcutaneous Panc-1, BxPC-3, and MIA PaCa-2 tumors became fluorescent after intravenous administration of fluorescent IGF-1R antibodies. Orthotopically-transplanted BxPC-3 tumors became fluorescent with the conjugated IGF-1R antibodies, and were easily visible with intravital imaging. Gross and microscopic ex vivo imaging of resected pancreatic tumor and normal pancreas confirmed that fluorescence indeed came from the membrane of cancer cells, and it was stronger from the tumor than the normal tissue. The present study demonstrates that fluorophore-conjugated IGF-1R antibodies can visualize pancreatic cancer and it can be used with various imaging devices such as endoscopy and laparoscopy for diagnosis and fluorescence-guided surgery. PMID:26919100

  18. Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model.

    PubMed

    Murakami, Takashi; DeLong, Jonathan; Eilber, Fritz C; Zhao, Ming; Zhang, Yong; Zhang, Nan; Singh, Arun; Russell, Tara; Deng, Samantha; Reynoso, Jose; Quan, Cuong; Hiroshima, Yukihiko; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Chawla, Sant; Endo, Itaru; Hoffman, Robert M

    2016-03-15

    A patient with high grade undifferentiated pleomorphic soft-tissue sarcoma from a striated muscle was grown orthotopically in the right biceps femoris muscle of mice to establish a patient-derived orthotopic xenograft (PDOX) model. Twenty PDOX mice were divided into 4 groups: G1, control without treatment; G2, Salmonella typhimurium (S. typhimurium)A1-R administered by intratumoral (i.t.) injection once a week for 4 weeks; G3, doxorubicin (DOX) administered by intraperitoneal (i.p.) injection once a week for 4 weeks; G4, S. typhimurium A1-R (i.t.) administered once a week for 2 weeks followed by i.p. doxorubicin once a week for 2 weeks. On day 25 from the initiation of treatment, tumor volume in G2, G3, and G4 was significantly lower than G1. Mice found without gross tumor included one mouse (20%) in G2; one mouse (20%) in G3; and 3 mice (60%) in G4. Body weight loss did not significantly differ between the 3 treated groups or from the untreated control. Histological examination revealed eradication of tumor only in G4 where mice were treated with S. typhimurium A1-R followed by DOX. Our present study indicates future clinical potential of combining S. typhimurium A1-R with chemotherapy such as DOX for soft tissue sarcoma patients.

  19. Establishment of a patient-derived orthotopic Xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern.

    PubMed

    Hiroshima, Yukihiko; Zhang, Yong; Zhang, Nan; Maawy, Ali; Mii, Sumiyuki; Yamamoto, Mako; Uehara, Fuminari; Miwa, Shinji; Yano, Shuya; Murakami, Takashi; Momiyama, Masashi; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Murata, Takuya; Endo, Itaru; Hoffman, Robert M

    2015-01-01

    Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient's cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient's cervical tumors resulted in primary growth but not metastasis.

  20. 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…

  1. 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...

  2. Insect biotechnology: controllable replacement of disease vectors.

    PubMed

    Wimmer, Ernst A

    2013-05-20

    To fight human vector-borne diseases, first releases of sterile transgenic mosquitoes have been performed. Someday, disease-refractory mosquitoes will replace wild types to stop transmission. For such population replacements, gene drive mechanisms must be established that allow local confinement and reversibility.

  3. 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...

  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...

  5. 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...

  6. 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...

  7. 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...

  8. Condylar hyperplasia following unilateral temporomandibular joint replacement.

    PubMed

    Machon, V; Levorova, J; Hirjak, D; Foltan, R

    2015-06-01

    Total joint replacement of the temporomandibular joint (TJR) can be associated with intraoperative and postoperative complications. We report herein the occurrence of a postoperative open bite malocclusion, the result of condylar hyperplasia affecting the non-operated joint at 1 year after unilateral total joint replacement. PMID:25662429

  9. Conservative treatment planning in veneer replacement.

    PubMed

    Guzmán-Armstrong, Sandra; Maia, Rodrigo Rocha

    2016-04-01

    This clinical report describes a conservative treatment in veneer replacement where diastemas, malalignment, and midline shift were the main modifying factors. When replacement veneers are indicated, the definitive results can only be accurately predicted after an esthetic reanalysis of the existing restorations. PMID:26602148

  10. International variation in hip replacement rates

    PubMed Central

    Merx, H; Dreinhofer, K; Schrader, P; Sturmer, T; Puhl, W; Gunther, K; Brenner, H

    2003-01-01

    Objectives: To summarise epidemiological data on the frequency of hip replacements in the countries of the developed world, especially in countries of the Organisation for Economic Cooperation and Development (OECD), and to investigate whether missing consensus criteria for the indication for total hip replacement (THR) result in different replacement rates. Methods: Country-specific hip replacement rates were collected using the available literature, different data sources of national authorities, and estimates of leading hip replacement manufacturers. Results: According to administrative and literature data sources the reported crude primary THR rate varied between 50 and 130 procedures/100 000 inhabitants in OECD countries in the 1990s. The crude overall hip implantation rate, summarising THR, partial hip replacement, and hip revision procedures, was reported to range from 60 to 200 procedures/100 000 inhabitants in the late 1990s. Moreover, large national differences were seen in the relationship between total and partial hip replacement procedures. Conclusion: The reported differences in hip replacement rates in OECD countries are substantial. They may be due to various causes, including different coding systems, country-specific differences in the healthcare system, in total expenditure on health per capita, in the population age structure, and in different indication criteria for THR. PMID:12594106

  11. 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...

  12. 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...

  13. 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.

  14. Transurethral biopsy of the prostatic urethra is associated with final apical margin status at radical cystoprostatectomy

    PubMed Central

    von Rundstedt, Friedrich-Carl; Mata, Douglas A; Shen, Steven; Li, Yi; Godoy, Guilherme; Lerner, Seth P

    2015-01-01

    Purpose Biopsy of the prostatic urethra is an integral part of clinical staging in patients prior to radical cystoprostatectomy (RC) and urinary diversion. We examined whether preoperative transurethral resection (TUR) biopsy was associated with final apical urethral margin status and hypothesized that a negative biopsy could replace intraoperative frozen section for decision making regarding the feasibility of orthotopic neobladder reconstruction. Methods TUR biopsy, frozen section, urethrectomy, and final apical urethral margin pathologic data were extracted from the charts of men who had undergone RC at the Houston Methodist Hospital between 1987 and 2013. TUR biopsies were performed at five and seven o’clock adjacent to the verumontanum. A positive biopsy was defined as the presence of in situ or invasive urothelial carcinoma. Clinical and perioperative variables were analyzed using descriptive and inferential statistics. Results We reviewed the medical records of 272 men. Preoperative TUR biopsies of the prostatic urethra were negative in 74% (200/272) and positive in 26% (72/272) of men. The overall incidence of apical urethral margin positivity on final pathology was 2.2% (six of 272). Four men underwent primary or secondary urethrectomy. TUR biopsy negative and positive predictive values for apical urethral margin positivity were 99.5% (95% confidence interval (CI): 97.2 to 99.9) and 6.9% (95% CI: 2.3 to 15.5), respectively. Conclusions The incidence of a positive apical urethral margin was low in patients undergoing RC. A negative preoperative TUR biopsy of the prostatic urethra was reliably associated with a negative final margin, obviating the need for intraoperative frozen section. Furthermore, a positive biopsy was not reliably associated with final margin status. These data will aid in the counseling of patients regarding the feasibility of neobladder reconstruction.

  15. Older Person's Guide to Joint Replacement

    MedlinePlus

    ... he or she will refer you to an orthopedic surgeon who does hip and knee replacement surgery. ... The Arthritis Foundation Web The American Academy of Orthopedic Surgeons ' The American Association of Knee and Hip ...

  16. Replacement Saltwell Pumping System Document Bibliography

    SciTech Connect

    BELLOMY, J.R.

    2000-12-07

    This document bibliography is prepared to identify engineering documentation developed during the design of the Replacement Saltwell Pumping System. The bibliography includes all engineering supporting documents and correspondence prepared prior to the deployment of the system in the field. All documents referenced are available electronically through the Records Management Information System (RMIS). Major components of the Replacement Saltwell Pumping System include the Sundyne Canned Motor Pump, the Water Filter Skid, the Injection Water Skid and the Backflow Preventer Assembly. Drawing H-14-104498 provides an index of drawings (fabrication details, P&IDs, etc.) prepared to support development of the Replacement Saltwell Pumping System. Specific information pertaining to new equipment can be found in Certified Vendor Information (CVI) File 50124. This CVI file has been established specifically for new equipment associated with the Replacement Saltwell Pumping System.

  17. Bioceramics in ossicular replacement prostheses: a review.

    PubMed

    Wongwiwat, Plawut; Boonma, Apichart; Lee, Yuan-Shin; Narayan, Roger J

    2011-01-01

    For many decades, bioceramic materials have been used in a variety of biomedical applications due to their biocompatibility, hardness, wear resistance and compressive strength properties. Bioceramic materials, including Bioglass, glass ceramic materials, and hydroxyapatite, have used to create total ossicular replacement prostheses and partial ossicular replacement prostheses. This review describes design factors associated with middle ear implants as well as clinical use of bioceramic materials in middle ear implants.

  18. Annual report for Ion Replacement Program

    SciTech Connect

    Tomczuk, Z.; Willit, J.L.; Fischer, A.K.

    1993-07-01

    Ion replacement electrorefining is an innovative electrochemical approach to purifying and separating metals. This approach overcomes the shortcomings of conventional electrorefining and has the potential for processing a wider range of metals and metal halide salts. Salt waste is also minimized with this approach. The key element of ion replacement electrorefining is the ion replacement electrode. This electrode allows a decoupling of the electrotransport process into two separate steps, anodic dissolution and cathodic deposition. Three key accomplishments described in this report that demonstrate the feasibility of ion replacement electrorefining are: (1) we have identified a suitable sodium/{beta}{double_prime}-alumina/molten salt electrolyte system that functions reproducibly at 723 K, (2) we have oxidized and deposited dysprosium, lanthanum, uranium, and titanium by using a sodium ion replacement electrode. In several experiments, an actual separation of dysprosium and lanthanum was observed, and (3) we have identified a metal alloy, Li{sub x}Sb, as an alternative ion replacement electrode. The next stage in the program is the design, construction, and testing of a laboratory-scale electrorefiner. Follow-on development with funding from industrial and federal sponsors is being pursued.

  19. A replaceable reflective film for solar concentrators

    SciTech Connect

    Not Available

    1991-09-01

    The 3M Company manufactures a silvered acrylic film called ECP-305 that is regarded as the preferred reflective film for use on stretched-membrane heliostats. However, ECP-305 will degrade in time, due to both corrosion of the silver layer and delamination at the film's silver-to-acrylic interface, and will eventually need to be replaced. 3M uses a very aggressive adhesive on this film, and once it is laminated, replacement is very difficult. The purpose of this investigation was the development of a replaceable reflector, a reflective film that can be easily removed and replaced. A replaceable reflector was successfully configured by laminating ECP-305 to the top surface of a smooth, dimensionally stable polymer film, with a removable adhesive applied to the underside of the polymer film. Several stages of screening and testing led to the selection of a 0.010-inch thick polycarbonate (GE 8030) as the best polymer film and a medium tack tape (3M Y-9425) was selected as the best removable adhesive. To demonstrate the feasibility of the replaceable reflector concept and to provide a real-time field test, the chosen construction was successfully applied to the 50-m{sup 2} SKI heliostat at the Central Receiver Test Facility at Sandia National Laboratories in Albuquerque. 4 refs., 13 figs., 7 tabs.

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

    SciTech Connect

    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

    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 CT (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.

  1. 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

  2. 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

  3. Effects of Dexmedetomidine on Postoperative Cognitive Dysfunction and Serum Levels of b-Amyloid and Neuronal Microtubule-Associated Protein in Orthotopic Liver Transplantation Patients.

    PubMed

    Xu, Guang; Li, Lan-Lan; Sun, Zhen-Tao; Zhang, Wei; Han, Xue-Ping

    2016-01-01

    BACKGROUND Because of the restricted data available on patients with postoperative cognitive dysfunction (POCD) in orthotopic liver transplantation (OLT), the goal of our study was to determine the outcome of dexmedetomidine (DEX) on POCD and the mechanism operating in OLT patients. MATERIAL AND METHODS Our study included 80 patients randomly divided into 2 equal groups: the DEX group and the control group. In the DEX group, our patients received an initial dose of DEX at 1 µg/kg for 10 min followed by a continuous infusion at 0.3 µg/kg/h until the end of surgery. The control group received a saline treatment, and neurological tests were performed to assess the status of POCD. Serum level of b-amyloid protein (Aβ) and neuronal microtubule-associated protein (Tau) were measured at designated time points: at pre-operation (T1), 0.5 h after the anhepatic phase (T2), 2 h after the reperfusion of the new liver (T3), at the completion of operation (T4), at day 1 (T5), and at day 7 (T6) after the operation. RESULTS The incidence of POCD was significantly reduced in the DEX group (P=0.017). The score from the neurological tests was significantly decreased in the control group after the operation, but no statistical difference was observed in the DEX group. The DEX groups demonstrated a lower level of β-amyloid and Tau protein than those at the corresponding time points (T4~T6) in the control group (P<0.01). CONCLUSIONS Dexmedetomidine reduced the incidence of postoperative cognitive dysfunction in orthotopic liver transplantation patients. The decreased levels of b-amyloid and Tau protein may have contributed to this favorable outcome. PMID:27527391

  4. Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats.

    PubMed

    Yao, Hui; Chi, Xinjin; Jin, Yi; Wang, Yiheng; Huang, Pinjie; Wu, Shan; Xia, Zhengyuan; Cai, Jun

    2015-11-20

    Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-кB(NF-кB) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-κB, tumor necrosis factor-α, and interleukin-1β levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-κB, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using α2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-κB pathway activation. The renoprotective effects are related to α2A-adrenergic receptor subtypes.

  5. Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue.

    PubMed

    Chen, Chien-Chang; Lin, Wei-Chuan; Kong, Man-Shan; Shi, Hai Ning; Walker, W Allan; Lin, Chun-Yen; Huang, Ching-Tai; Lin, Yung-Chang; Jung, Shih-Ming; Lin, Tzou-Yien

    2012-06-01

    Modulation of the cellular response by the administration of probiotic bacteria may be an effective strategy for preventing or inhibiting tumour growth. We orally pre-inoculated mice with probiotics Lactobacillus acidophilus NCFM (La) for 14 d. Subcutaneous dorsal-flank tumours and segmental orthotopic colon cancers were implanted into mice using CT-26 murine colon adenocarcinoma cells. On day 28 after tumour initiation, the lamina propria of the colon, mesenteric lymph nodes (MLN) and spleen were harvested and purified for flow cytometry and mRNA analyses. We demonstrated that La pre-inoculation reduced tumour volume growth by 50·3 %, compared with untreated mice at 28 d after tumour implants (2465·5 (SEM 1290·4) v. 4950·9 (SEM 1689·3) mm³, P<0·001). Inoculation with La reduced the severity of colonic carcinogenesis caused by CT-26 cells, such as level of colonic involvement and structural abnormality of epithelial/crypt damage. Moreover, La enhanced apoptosis of CT-26 cells both in dorsal-flank tumour and segmental orthotopic colon cancer, and the mean counts of apoptotic body were higher in mice pre-inoculated with La (P<0·05) compared with untreated mice. La pre-inoculation down-regulated the CXCR4 mRNA expressions in the colon, MLN and extra-intestinal tissue, compared with untreated mice (P<0·05). In addition, La pre-inoculation reduced the mean fluorescence index of MHC class I (H-2Dd, -Kd and -Ld) in flow cytometry analysis. Taken together, these findings suggest that probiotics La may play a role in attenuating tumour growth during CT-26 cell carcinogenesis. The down-regulated expression of CXCR4 mRNA and MHC class I, as well as increasing apoptosis in tumour tissue, indicated that La may be associated with modulating the cellular response triggered by colon carcinogenesis. PMID:21992995

  6. Boswellic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in Orthotopic Mouse Model By Downregulating Inflammatory, Proliferative, Invasive, and Angiogenic Biomarkers

    PubMed Central

    Yadav, Vivek R.; Prasad, Sahdeo; Sung, Bokyung; Gelovani, Juri G.; Guha, Sushovan; Krishnan, Sunil; Aggarwal, Bharat B.

    2011-01-01

    Numerous cancer therapeutics were originally identified from natural products used in traditional medicine. One such agent is acetyl-11-keto-beta-boswellic acid (AKBA), derived from the gum resin of the Boswellia serrata known as Salai guggal or Indian frankincense. Traditionally it has been used in Ayurvedic medicine to treat proinflammatory conditions. In the present report, we hypothesized that AKBA can affect the growth and metastasis of colorectal cancer (CRC) in orthotopically-implanted tumors in nude mice. We found that the oral administration of AKBA (50-200 mg/kg) dose-dependently inhibited the growth of CRC tumors in mice, resulting in decrease in tumor volumes than those seen in vehicle-treated mice without significant decreases in body weight. In addition, we observed that AKBA was highly effective in suppressing ascites and distant metastasis to the liver, lungs, and spleen in orthotopically-implanted tumors in nude mice. When examined for the mechanism, we found that markers of tumor proliferation index Ki-67 and the microvessel density CD31; were significantly downregulated by AKBA treatment. We also found that AKBA significantly suppressed NF-κB activation in the tumor tissue and expression of pro-inflammatory (COX2), tumor survival (bcl-2, bcl-xL, IAP-1, survivin), proliferative (cyclin D1), invasive (ICAM-1, MMP-9) and angiogenic (CXCR4 and VEGF) biomarkers. When examined for serum and tissue levels of AKBA, a dose-dependent increase in the levels of the drug was detected, indicating its bioavailability. Thus, our findings suggest that this boswellic acid analogue can inhibit the growth and metastasis of human CRC in vivo through downregulation of cancer-associated biomarkers. PMID:21702037

  7. 99mTc-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model

    PubMed Central

    2013-01-01

    Background Since proteoglycans (PGs) appear as key partners in chondrosarcoma biology, PG-targeted imaging using the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-NTP 15-5) developed by our group was previously demonstrated to be a good single-photon emission computed tomography tracer for cartilage neoplasms. We therefore initiated this new preclinical study to evaluate the relevance of 99mTc-NTP 15-5 imaging for the in vivo monitoring and quantitative assessment of chondrosarcoma response to zoledronic acid (ZOL) in the Swarm rat orthotopic model. Findings Rats bearing chondrosarcoma in the orthotopic paratibial location were treated by ZOL (100 μg/kg, subcutaneously) or phosphate-buffered saline, twice a week, from day 4 to day 48 post-tumor implantation. 99mTc-NTP 15-5 imaging was performed at regular intervals with the target-to-background ratio (TBR) determined. Tumor volume was monitored using a calliper, and histology was performed at the end of the study. From day 11 to day 48, mean TBR values ranged from 1.7 ± 0.6 to 2.3 ± 0.6 in ZOL-treated rats and from 2.1 ± 1.0 to 4.9 ± 0.9 in controls. Tumor growth inhibition was evidenced using a calliper from day 24 and associated to a decrease in PG content in treated tumor tissues (confirmed by histology). Conclusions This work demonstrated two proofs of concept: (1) biphosphonate therapy could be a promising therapeutic approach for chondrosarcoma; (2) 99mTc-NTP 15-5 is expected to offer a novel imaging modality for the in vivo evaluation of the extracellular matrix features of chondrosarcoma, which could be useful for the follow-up and quantitative assessment of proteoglycan ‘downregulation’ associated to the response to therapeutic attempts. PMID:23688107

  8. Kittiwakes strategically reduce investment in replacement clutches

    USGS Publications Warehouse

    Gasparini, J.; Roulin, A.; Gill, V.A.; Hatch, Shyla A.; Boulinier, T.

    2006-01-01

    Many life-history traits are expressed interactively in life, but to a varying extent on different occasions. Changes in trait expression can be accounted for by differences in the quality of the environment ('environmental constraint' hypothesis) or by strategic adjustments, if the relative contribution of the trait to fitness varies with time ('strategic allocation' hypothesis). In birds, egg production is lower in replacement clutches than in first clutches, but it is unknown whether this reduction results from an environmental constraint (e.g. food being less available at the time when the replacement clutch is produced) or from a strategic allocation of resources between the two breeding attempts. To distinguish between these two hypotheses, we performed an experiment with black-legged kittiwakes (Rissa tridactyla). Pairs were either food-supplemented or not before the first clutch was laid onwards and we induced them to produce a replacement clutch by removing eggs once when the first clutch was complete. As predicted by the 'strategic allocation' hypothesis, egg production of food-supplemented and non-food-supplemented birds decreased between first and replacement clutches. This suggests that kittiwakes strategically reduce investment in egg production for their replacement clutches compared to first clutches. ?? 2006 The Royal Society.

  9. Nashville Gas treads carefully to replace pipe

    SciTech Connect

    1997-06-01

    The private gas utility, Nashville Gas, was responsible for replacing damaged or inadequate 2- and 4-inch steel gas lines beneath Music City, USA. The line replacements required either size for size or upsizing. The first choice was directional drilling, which was quickly determined to be unpractical because of rocky soil conditions. The second option was open trenching. Undoubtedly, trenching would mean having to contend with angry residents and tourists, since gas lines ran beneath yards, mature trees, sidewalks, roadways, and railways. In addition to the negative social factors, trenching would require additional funds for substantial landscaping and pavement replacement. It at all possible, a no-dig alternative was desired. Nashville Gas found Grundomat piercing tools which create a bore, then pushes pipe back through it. These same tools can simultaneously pull in pipe. These tools were customized for the Nashville project.

  10. Adaptive Replacement Strategies for MOEA/D.

    PubMed

    Wang, Zhenkun; Zhang, Qingfu; Zhou, Aimin; Gong, Maoguo; Jiao, Licheng

    2016-02-01

    Multiobjective evolutionary algorithms based on decomposition (MOEA/D) decompose a multiobjective optimization problem into a set of simple optimization subproblems and solve them in a collaborative manner. A replacement scheme, which assigns a new solution to a subproblem, plays a key role in balancing diversity and convergence in MOEA/D. This paper proposes a global replacement scheme which assigns a new solution to its most suitable subproblems. We demonstrate that the replacement neighborhood size is critical for population diversity and convergence, and develop an approach for adjusting this size dynamically. A steady-state algorithm and a generational one with this approach have been designed and experimentally studied. The experimental results on a number of test problems have shown that the proposed algorithms have some advantages. PMID:25826813

  11. Replacement of charcoal sorbent in the VOST

    SciTech Connect

    Johnson, L.D.; Fuerst, R.G.; Foster, A.L.; Bursey, J.T.

    1993-01-01

    EPA Method 0030, the Volatile Organic Sampling Train (VOST), for sampling volatile organics from stationary sources, specifies the use of petroleum-base charcoal in the second sorbent tube. Charcoal has proven to be a marginal performer as a sampling sorbent, partly due to inconsistency in analyte recovery. In addition, commercial availability of petroleum charcoal for VOST tubes has been variable. Lack of data on comparability and variability of charcoals for VOST application has created uncertainty when other charcoals are substituted. Five potential sorbent replacements for charcoal in Method 0030 were evaluated along with a reference charcoal. Two of the sorbents tested, Ambersorb XE-340 and Tenax GR, did not perform well enough to qualify as replacements. Three candidates, Anasorb 747, Carbosieve S-III and Kureha Beaded Activated Charcoal, performed adequately, and produced statistically equivalent results. Anasorb 747 appears to be an acceptable replacement for petroleum charcoal, based on a combination of performance, availability, and cost.

  12. Phaser.MRage: automated molecular replacement

    SciTech Connect

    Bunkóczi, Gábor; McCoy, Airlie J.; Oeffner, Robert D.; Read, Randy J.

    2013-11-01

    The functionality of the molecular-replacement pipeline phaser.MRage is introduced and illustrated with examples. Phaser.MRage is a molecular-replacement automation framework that implements a full model-generation workflow and provides several layers of model exploration to the user. It is designed to handle a large number of models and can distribute calculations efficiently onto parallel hardware. In addition, phaser.MRage can identify correct solutions and use this information to accelerate the search. Firstly, it can quickly score all alternative models of a component once a correct solution has been found. Secondly, it can perform extensive analysis of identified solutions to find protein assemblies and can employ assembled models for subsequent searches. Thirdly, it is able to use a priori assembly information (derived from, for example, homologues) to speculatively place and score molecules, thereby customizing the search procedure to a certain class of protein molecule (for example, antibodies) and incorporating additional biological information into molecular replacement.

  13. [Update in continuous renal replacement techniques].

    PubMed

    Romero-García, M; de la Cueva-Ariza, L; Delgado-Hito, P

    2013-01-01

    Acute renal failure affects 25% of patients hospitalized in intensive care units. Despite technological advances, the mortality of these patients is still high due to its associated complications. Continuous renal replacement techniques are one of the treatments for acute renal failure because they make it possible to treat the complications and decrease mortality. The nurse's knowledge and skills regarding these techniques will be decisive for the success of the therapy. Consequently, the nurse's experience and training are key components. The objective of this article is to update the knowledge on continuous renal replacement techniques. Keeping this in mind, a review has been made of the physical and chemical principles such as diffusion and convection, among others. A description of the different continuous renal replacement techniques, a presentation of the main vascular access, and a description of the nursing cares and complications related to techniques used have also been provided.

  14. Rapid prototyping of ossicular replacement prostheses

    NASA Astrophysics Data System (ADS)

    Ovsianikov, A.; Chichkov, B.; Adunka, O.; Pillsbury, H.; Doraiswamy, A.; Narayan, R. J.

    2007-05-01

    Materials used in ossicular replacement prostheses must demonstrate appropriate biological compatibility, acoustic transmission, stability, and stiffness properties. Prostheses prepared using Teflon ®, titanium, Ceravital and other conventional materials have demonstrated several problems, including migration, perforation of the tympanic membrane, difficulty in shaping the prostheses, and reactivity with the surrounding tissues. We have used two-photon polymerization for rapid prototyping of Ormocer ® middle-ear bone replacement prostheses. Ormocer ® surfaces fabricated using two-photon polymerization exhibited acceptable cell viability and cell growth profiles. The Ormocer ® prosthesis was able to be inserted and removed from the site of use in the frozen human head without fracture. Our results demonstrate that two-photon polymerization is able to create ossicular replacement prostheses and other medical devices with a larger range of sizes, shapes and materials than other microfabrication techniques.

  15. 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. PMID:19547086

  16. The echocardiography of replacement heart valves

    PubMed Central

    2016-01-01

    This is a practical description of how replacement valves are assessed using echocardiography. Normal transthoracic appearances including normal variants are described. The problem of differentiating normal function, patient–prosthesis mismatch and pathological obstruction in aortic replacement valves with high gradients is discussed. Obstruction and abnormal regurgitation is described for valves in the aortic, mitral and right-sided positions and when to use echocardiography in suspected infective endocarditis. The roles of transoesophageal and stress echocardiography are described and finally when other imaging techniques may be useful. PMID:27600454

  17. WEIGHT LOSS WITH MEAL REPLACEMENT AND MEAL REPLACEMENT PLUS SNACKS: A RANDOMIZED TRIAL

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To evaluate whether snacking would improve weight loss and weight maintenance in overweight individuals within the context of a structured meal replacement (MR) weight loss program. A prospective 24 week, 2 (snacking vs nonsnacking) x 2 (MR vs meal replacement augmented with snacks (MRPS)...

  18. 48 CFR 8.715 - Replacement commodities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Replacement commodities. 8.715 Section 8.715 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition From Nonprofit Agencies Employing People...

  19. A Helix Replacement Mechanism Directs Metavinculin Functions

    SciTech Connect

    Rangarajan, Erumbi S.; Lee, Jun Hyuck; Yogesha, S.D.; Izard, Tina

    2010-10-11

    Cells require distinct adhesion complexes to form contacts with their neighbors or the extracellular matrix, and vinculin links these complexes to the actin cytoskeleton. Metavinculin, an isoform of vinculin that harbors a unique 68-residue insert in its tail domain, has distinct actin bundling and oligomerization properties and plays essential roles in muscle development and homeostasis. Moreover, patients with sporadic or familial mutations in the metavinculin-specific insert invariably develop fatal cardiomyopathies. Here we report the high resolution crystal structure of the metavinculin tail domain, as well as the crystal structures of full-length human native metavinculin (1,134 residues) and of the full-length cardiomyopathy-associated {Delta}Leu954 metavinculin deletion mutant. These structures reveal that an {alpha}-helix (H1{prime}) and extended coil of the metavinculin insert replace {alpha}-helix H1 and its preceding extended coil found in the N-terminal region of the vinculin tail domain to form a new five-helix bundle tail domain. Further, biochemical analyses demonstrate that this helix replacement directs the distinct actin bundling and oligomerization properties of metavinculin. Finally, the cardiomyopathy associated {Delta}Leu954 and Arg975Trp metavinculin mutants reside on the replaced extended coil and the H1{prime} {alpha}-helix, respectively. Thus, a helix replacement mechanism directs metavinculin's unique functions.

  20. [Exoprosthetic Replacement of the Upper Extremity].

    PubMed

    Salminger, S; Mayer, J A; Sturma, A; Riedl, O; Bergmeister, K D; Aszmann, O C

    2016-08-01

    During the last years, the prosthetic replacement in upper limb amputees has undergone different developments. The use of new nerve surgical concepts improved the control strategies tremendously, especially for high-level amputees. Technological innovation in the field of pattern recognition enables the control of multifunctional myoelectric hand prostheses in a natural and intuitive manner. However, the different levels of amputation pose different challenges for the therapeutic team which concern not only the prosthetic attachment; also the expected functional outcome of prosthetic limb replacement differs greatly between the individual levels of amputation. Therefore, especially in partial hand amputations the indication for prosthetic fitting has to be evaluated critically, as these patients may benefit more from biologic reconstructive concepts. The value of the upper extremity, in particular of the hand, is undisputable and, as such represents the driving force for the technological and surgical developments within the exoprosthetic replacement. This article discusses the possibilities and limitations of exoprosthetic limb replacement on the different amputation levels and explores new developments. PMID:27547980

  1. 30 CFR 57.19122 - Replacement parts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Personnel Hoisting Inspection and Maintenance § 57.19122 Replacement parts. Parts used to repair hoists shall have...

  2. 30 CFR 56.19122 - Replacement parts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personnel Hoisting Inspection and Maintenance § 56.19122 Replacement parts. Parts used to repair hoists shall have...

  3. SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

    EPA Science Inventory

    The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.

    Didecyldimethylammonium chloride [DDAC] was...

  4. Retrograde replacement of the thoracic aorta.

    PubMed Central

    Cooley, D A

    1995-01-01

    A technique is described for replacement of the entire thoracic aorta. In this "pull-through" technique, which utilizes hypothermic circulatory arrest, the graft is implanted in a retrograde fashion, thus providing protection for the spinal cord and brain and avoiding injury to the vagus and phrenic nerves. PMID:7647599

  5. Nicotine Replacement: Effects on Postcessation Weight Gain.

    ERIC Educational Resources Information Center

    Gross, Janet; And Others

    1989-01-01

    Examined nicotine replacement effects on postcessation weight gain in smoking cessation volunteers. Randomly assigned abstinent subjects to active nicotine or placebo gum conditions for 10 weeks. Analyses revealed strong evidence for gum effect on weight gain, with active gum users gaining mean total of 3.8 pounds compared with 7.8 pounds for…

  6. Do Formal Supports Replace Informal Supports?

    ERIC Educational Resources Information Center

    Barer, Barbara M.; And Others

    Health policy researchers have long been interested in the extent to which the provision of formal supports replaces or undermines the informal support system. This study examined the linkages between the formal and informal support system as they are mediated by a health care setting which readily provides patients with access to social services.…

  7. 30 CFR 56.19122 - Replacement parts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personnel Hoisting Inspection and Maintenance § 56.19122 Replacement parts. Parts used to repair hoists shall have...

  8. 30 CFR 56.19122 - Replacement parts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personnel Hoisting Inspection and Maintenance § 56.19122 Replacement parts. Parts used to repair hoists shall have...

  9. 30 CFR 57.19122 - Replacement parts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Personnel Hoisting Inspection and Maintenance § 57.19122 Replacement parts. Parts used to repair hoists shall have...

  10. 30 CFR 57.19122 - Replacement parts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Personnel Hoisting Inspection and Maintenance § 57.19122 Replacement parts. Parts used to repair hoists shall have...

  11. Probability Issues in without Replacement Sampling

    ERIC Educational Resources Information Center

    Joarder, A. H.; Al-Sabah, W. S.

    2007-01-01

    Sampling without replacement is an important aspect in teaching conditional probabilities in elementary statistics courses. Different methods proposed in different texts for calculating probabilities of events in this context are reviewed and their relative merits and limitations in applications are pinpointed. An alternative representation of…

  12. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2014-01-01 2013-01-01 true Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  13. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2010-01-01 2009-01-01 true Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  14. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2011-01-01 2009-01-01 true Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  15. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED)...

  16. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2012-01-01 2012-01-01 false Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  17. Aggression Replacement Training and Childhood Trauma

    ERIC Educational Resources Information Center

    Amendola, A. Mark; Oliver, Robert W.

    2013-01-01

    Aggression Replacement Training (ART) was developed by the late Arnold Goldstein of Syracuse University to teach positive alternatives to children and youth with emotional and behavioral problems (Glick & Gibbs, 2011; Goldstein, Glick, & Gibbs, 1998). ART provides cognitive, affective, and behavioral interventions to build competence in…

  18. Measure Guideline: Window Repair, Rehabilitation, and Replacement

    SciTech Connect

    Baker, P.

    2012-12-01

    This measure guideline provides information and guidance on rehabilitating, retrofitting, and replacing existing window assemblies in residential construction. The intent is to provide information regarding means and methods to improve the energy and comfort performance of existing wood window assemblies in a way that takes into consideration component durability, in-service operation, and long term performance of the strategies.

  19. REPLACING SOLVENT CLEANING WITH AQUEOUS CLEANING

    EPA Science Inventory

    The report documents actions taken by Robert Bosch Corp., Charleston, SC, in replacing the cleaning solvents 1, 1, 2- trichloro-1, 2, 2-trifluoroethane (CFC-113) and trichloroethylene (TCE) with aqueous solutions. Bosch has succeeded in eliminating all their CFC-113 use and so f...

  20. 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.

  1. A replaceable reflective film for solar concentrators

    NASA Astrophysics Data System (ADS)

    1991-09-01

    The 3M Company manufactures a silvered acrylic film called ECP-305 that is regarded as the preferred reflective film for use on stretched-membrane heliostats. However, ECP-305 will degrade in time, due to both corrosion of the silver layer and delamination at the film's silver-to-acrylic interface. The purpose of this investigation was the development of a replaceable reflector, a reflective film that can be easily removed and replaced. A replaceable reflector was successfully configured by laminating ECP-305 to the top surface of a smooth, dimensionally stable polymer film, with a removable adhesive applied to the underside of the polymer film. Several stages of screening and testing led to the selection of a 0.010-inch thick polycarbonate as the best polymer film and a medium tack tape was selected as the best removable adhesive. To demonstrate the feasibility of the replaceable reflector concept and to provide a real time field test, the chosen construction was successfully applied to the 50 sq m SKI heliostat at Sandia National Laboratories in Albuquerque.

  2. Mineral replacement front propagation in deformed rocks

    NASA Astrophysics Data System (ADS)

    Beaudoin, Nicolas; Koehn, Daniel; Kelka, Ulrich

    2015-04-01

    Fluid migrations are a major agent of contaminant transport leading to mineral replacement in rocks, impacting their properties as porosity, permeability, and rheology. Understanding the physical and chemical mechanisms that govern mineralogical replacement during and after deformation is required to better understand complex interplays between fluid and rocks that are involved in faulting, seismic cycle, and resource distribution in the upper crust. Dolomitization process related to hydrothermal fluid flow is one of the most studied and debated replacement processes in earth sciences. Dolomitization of limestone is of economic importance as well, as it stands as unconventional oil reservoirs and is systematically observed in Mississippian-Valley Type ore deposit. Despite recent breakthrough about dolomitization processes at large-scale, the small-scale propagation of the reaction front remains unclear. It is poorly documented in the occurrence of stylolites and fractures in the medium while pressure-solution and fracture network development are the most efficient deformation accomodation mechanism in limestone from early compaction to layer-parallel shortening. Thus, the impact of such network on geometry of replaced bodies and on replacement front propagation deserves specific attention. This contribution illustrates the role of fracture and stylolites on the propagation of a reaction front. In a 2 dimensional numerical model we simulate the dolomitization front propagation in a heterogeneous porous medium. The propagation of the reaction front is governed by the competition between advection and diffusion processes, and takes into account reaction rates, disorder in the location of the potential replacement seeds, and permeability heterogeneities. We add stylolites and fractures that can act as barriers or drains to fluid flow according to their orientation and mineralogical content, which can or cannot react with the contaminant. The patterns produced from

  3. Coronary Ostial Stenosis after Aortic Valve Replacement

    PubMed Central

    Ziakas, Antonios G.; Economou, Fotios I.; Charokopos, Nicholas A.; Pitsis, Antonios A.; Parharidou, Despina G.; Papadopoulos, Thomas I.; Parharidis, Georgios E.

    2010-01-01

    Coronary ostial stenosis is a rare but potentially serious sequela after aortic valve replacement. It occurs in the left main or right coronary artery after 1% to 5% of aortic valve replacement procedures. The clinical symptoms are usually severe and may appear from 1 to 6 months postoperatively. Although the typical treatment is coronary artery bypass grafting, patients have been successfully treated by means of percutaneous coronary intervention. Herein, we present the cases of 2 patients in whom coronary ostial stenosis developed after aortic valve replacement. In the 1st case, a 72-year-old man underwent aortic valve replacement and bypass grafting of the saphenous vein to the left anterior descending coronary artery. Six months later, he experienced a non-ST-segment-elevation myocardial infarction. Coronary angiography revealed a critical stenosis of the right coronary artery ostium. In the 2nd case, a 78-year-old woman underwent aortic valve replacement and grafting of the saphenous vein to an occluded right coronary artery. Four months later, she experienced unstable angina. Coronary angiography showed a critical left main coronary artery ostial stenosis and occlusion of the right coronary artery venous graft. In each patient, we performed percutaneous coronary intervention and deployed a drug-eluting stent. Both patients were asymptomatic on 6-to 12-month follow-up. We attribute the coronary ostial stenosis to the selective ostial administration of cardioplegic solution during surgery. We conclude that retrograde administration of cardioplegic solution through the coronary sinus may reduce the incidence of postoperative coronary ostial stenosis, and that stenting may be an efficient treatment option. PMID:20844624

  4. Blood conservation strategies in cardiac valve replacement

    PubMed Central

    Zheng, Junnan; Chen, Liangwei; Qian, Linfeng; Jiang, Jianjie; Chen, Yinglian; Xie, Jue; Shi, Liping; Ni, Yiming; Zhao, Haige

    2016-01-01

    Abstract We aimed to evaluate whether blood conservation strategies including intraoperative autologous donation (IAD) could reduce perioperative blood transfusion for patients undergoing cardiac valve replacement including mitral valve replacement, aortic valve replacement (AVR), and double valve replacement (DVR). A total of 726 patients were studied over a 3-year period (2011–2013) after the implementation of IAD and were compared with 919 patients during the previous 36-month period (January 2008–December 2010). The method of small-volume retrograde autologous priming, strict blood transfusion standard together with IAD constituted a progressive blood-saving strategy. Baseline characteristics and preoperative information showed no statistically significant difference between IAD group and non-IAD group. Most of the postoperative morbidities are statistically the same in the 2 groups. Chest tube output (415.2 vs 1029.8 mL, P < 0.001) and postoperative respiratory failure (5.9% vs 8.6%, P = 0.039) favored the IAD group, whereas hematocrit levels were more favorable in the non-IAD group (30.3% vs 33.0% at the end of the operation, P < 0.001; 30.4% vs 31.5% at the time of discharge). The use of blood product transfusion was higher in the non-IAD group (22.6% vs 43.3%, P < 0.001). Binary multivariate logistic regression analysis showed that high age, non-IAD, DVR surgery, and absent smoking history are associated with a higher risk of intra-/postoperative blood transfusion. Blood conservation is effective and safe in cardiac valve replacement surgeries. The use of intraoperative autologous donation can lead to improved outcomes including a significantly lower rate of intra-/postoperative blood transfusion and postoperative complications. PMID:27741149

  5. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in 41 CFR 102-34.270 and 109-38.402. (b) The Heads of Contracting... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Replacement of...

  6. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in FPMR 41 CFR 101-38.9 and DOE-PMR 41 CFR 109-38.9. (b) The... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Replacement of...

  7. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in 41 CFR 102-34.270 and 109-38.402. (b) The Heads of Contracting... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Replacement of...

  8. 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 700.189 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement...

  9. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in FPMR 41 CFR 101-38.9 and DOE-PMR 41 CFR 109-38.9. (b) The... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Replacement of...

  10. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in FPMR 41 CFR 101-38.9 and DOE-PMR 41 CFR 109-38.9. (b) The... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Replacement of...

  11. 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...

  12. 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...

  13. 41 CFR 109-38.402 - Replacement standards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., AND MOTOR VEHICLES 38-MOTOR EQUIPMENT MANAGEMENT 38.4-Use and Replacement Standards § 109-38.402 Replacement standards. (a) (b) Motor vehicles may be replaced without regard to the replacement standards in 41 CFR 101-38.402 only after certification by the Director of Administrative Services or the Head...

  14. 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. PMID:27176787

  15. Mitochondrial replacement therapy in reproductive medicine.

    PubMed

    Wolf, Don P; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2015-02-01

    Mitochondrial dysfunction is implicated in disease and age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes, such as pronuclear (PNT), spindle (ST), or polar body (PBT) transfer, could prevent second-generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal development to adults and low mtDNA carryover. PBT in mice, coupled with PN or ST, may increase the yield of reconstructed embryos with low mtDNA carryover. MRT also offers replacement of the deficient cytoplasm in oocytes from older patients, with the expectation of high pregnancy rates following in vitro fertilization. PMID:25573721

  16. Mitochondrial Replacement Therapy in Reproductive Medicine

    PubMed Central

    Wolf, Don P.; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2015-01-01

    Mitochondrial dysfunction is implicated in disease and in age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes such as pronuclear (PNT), spindle (ST) or polar body (PBT) transfer could prevent second generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal development to adults and low mtDNA carryover. PBT in mice, coupled with PN or ST, may increase the yield of reconstructed embryos with low mtDNA carryover. MRT also offers replacement of the deficient cytoplasm in oocytes from older patients, with the expectation of high pregnancy rates following in vitro fertilization. PMID:25573721

  17. Enzyme replacement in Tay-Sachs disease.

    PubMed

    von Specht, B U; Geiger, B; Arnon, R; Passwell, J; Keren, G; Goldman, B; Padeh, B

    1979-06-01

    Enzyme replacement therapy was attempted with two Tay-Sachs-diseased individuals--a 14-month-old child and a 7-week-old infant. Treatment consisted of repeated weekly intrathecal injections of pure hexosaminidase A. Injection of this enzyme resulted in almost complete disappearance of GM2 from the serum, but did not bring about dissolution of the GM2 membranous cytoplasmic bodies in the brain, as detected by electronmicroscopy. Both patients tolerated the treatment without apparent clinical complications, but no clear-cut improvement was noted as a result of prolonged injections of hexosaminidase A. Since this treatment was initiated in both an advanced stage and a very early stage of the disease, we conclude that enzyme replacement treatment by this route is not beneficial for patients with Tay-Sachs disease. PMID:572006

  18. BALBES: a molecular-replacement pipeline

    SciTech Connect

    Long, Fei; Vagin, Alexei A.; Young, Paul; Murshudov, Garib N.

    2008-01-01

    The fully automated pipeline, BALBES, integrates a redesigned hierarchical database of protein structures with their domains and multimeric organization, and solves molecular-replacement problems using only input X-ray and sequence data. The number of macromolecular structures solved and deposited in the Protein Data Bank (PDB) is higher than 40 000. Using this information in macromolecular crystallography (MX) should in principle increase the efficiency of MX structure solution. This paper describes a molecular-replacement pipeline, BALBES, that makes extensive use of this repository. It uses a reorganized database taken from the PDB with multimeric as well as domain organization. A system manager written in Python controls the workflow of the process. Testing the current version of the pipeline using entries from the PDB has shown that this approach has huge potential and that around 75% of structures can be solved automatically without user intervention.

  19. Replacements For Ozone-Depleting Foaming Agents

    NASA Technical Reports Server (NTRS)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluorinated ethers used in processes as diverse as small batch pours, large sprays, or double-band lamination to make insulation for private homes, commercial buildings, shipping containers, and storage tanks. Fluorinated ethers proved useful as replacements for CFC refrigerants and solvents.

  20. Heart Valve Replacements with Regenerative Capacity

    PubMed Central

    Dijkman, Petra E.; Fioretta, Emanuela S.; Frese, Laura; Pasqualini, Francesco S.; Hoerstrup, Simon P.

    2016-01-01

    The incidence of severe valvular dysfunctions (e.g., stenosis and insufficiency) is increasing, leading to over 300,000 valves implanted worldwide yearly. Clinically used heart valve replacements lack the capacity to grow, inherently requiring repetitive and high-risk surgical interventions during childhood. The aim of this review is to present how different tissue engineering strategies can overcome these limitations, providing innovative valve replacements that proved to be able to integrate and remodel in pre-clinical experiments and to have promising results in clinical studies. Upon description of the different types of heart valve tissue engineering (e.g., in vitro, in situ, in vivo, and the pre-seeding approach) we focus on the clinical translation of this technology. In particular, we will deepen the many technical, clinical, and regulatory aspects that need to be solved to endure the clinical adaptation and the commercialization of these promising regenerative valves. PMID:27721704

  1. Total Hip Joint Replacement Biotelemetry System

    NASA Technical Reports Server (NTRS)

    Boreham, J. F.; Postal, R. B.; Luntz, R. A.

    1981-01-01

    The development of a biotelemetry system that is hermetically sealed within a total hip replacement implant is reported. The telemetry system transmits six channels of stress data to reconstruct the major forces acting on the neck of the prosthesis and uses an induction power coupling technique to eliminate the need for internal batteries. The activities associated with the telemetry microminiaturization, data recovery console, hardware fabrications, power induction systems, electrical and mechanical testing and hermetic sealing test results are discussed.

  2. The Anterior Approach for Total Hip Replacement.

    PubMed

    Hochfelder, Jason P; Davidovitch, Roy I

    2016-03-01

    The anterior approach for total hip replacements has recently gained popularity. Some authors report faster recoveries and decreased dislocation rated with no increased risk of complications. However others claim no difference in outcomes when compared to other approaches yet an increase in complication rates. This paper provides a brief history of the approach, discusses various indications and contraindications, preoperative considerations, surgical techniques, and postoperative protocols. PMID:26977549

  3. VH replacement in primary immunoglobulin repertoire diversification.

    PubMed

    Sun, Amy; Novobrantseva, Tatiana I; Coffre, Maryaline; Hewitt, Susannah L; Jensen, Kari; Skok, Jane A; Rajewsky, Klaus; Koralov, Sergei B

    2015-02-01

    The genes encoding the variable (V) region of the B-cell antigen receptor (BCR) are assembled from V, D (diversity), and J (joining) elements through a RAG-mediated recombination process that relies on the recognition of recombination signal sequences (RSSs) flanking the individual elements. Secondary V(D)J rearrangement modifies the original Ig rearrangement if a nonproductive original joint is formed, as a response to inappropriate signaling from a self-reactive BCR, or as part of a stochastic mechanism to further diversify the Ig repertoire. VH replacement represents a RAG-mediated secondary rearrangement in which an upstream VH element recombines with a rearranged VHDHJH joint to generate a new BCR specificity. The rearrangement occurs between the cryptic RSS of the original VH element and the conventional RSS of the invading VH gene, leaving behind a footprint of up to five base pairs (bps) of the original VH gene that is often further obscured by exonuclease activity and N-nucleotide addition. We have previously demonstrated that VH replacement can efficiently rescue the development of B cells that have acquired two nonproductive heavy chain (IgH) rearrangements. Here we describe a novel knock-in mouse model in which the prerearranged IgH locus resembles an endogenously rearranged productive VHDHJH allele. Using this mouse model, we characterized the role of VH replacement in the diversification of the primary Ig repertoire through the modification of productive VHDHJH rearrangements. Our results indicate that VH replacement occurs before Ig light chain rearrangement and thus is not involved in the editing of self-reactive antibodies.

  4. Risks of testosterone replacement therapy in men

    PubMed Central

    Osterberg, E. Charles; Bernie, Aaron M.; Ramasamy, Ranjith

    2014-01-01

    Testosterone replacement therapy (TRT) is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as cardioprotective effects, have been well-documented. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction. PMID:24497673

  5. Femoral Bone Plug in Total Knee Replacement.

    PubMed

    Vulcano, Ettore; Regazzola, Gianmarco M V; Murena, Luigi; Ronga, Mario; Cherubino, Paolo; Surace, Michele F

    2015-10-01

    The intramedullary alignment guides used in total knee replacement disrupt the intramedullary vessels, resulting in greater postoperative blood loss. The use of an autologous bone plug to seal the intramedullary femoral canal has been shown to be effective in reducing postoperative bleeding. The authors present a simple technique to create a bone plug from the anterior chamfer femoral cut to perfectly seal the intramedullary canal of the femur. PMID:26488774

  6. Biosurfactants: a sustainable replacement for chemical surfactants?

    PubMed

    Marchant, Roger; Banat, Ibrahim M

    2012-09-01

    Glycolipid biosurfactants produced by bacteria and yeasts provide significant opportunities to replace chemical surfactants with sustainable biologically produced alternatives in bulk commercial products such as laundry detergents and surface cleaners. Sophorolipids are already available in sufficient yield to make their use feasible while rhamnolipids and mannosylerythritol lipids require further development. The ability to tailor the biosurfactant produced to the specific needs of the product formulation will be an important future step. PMID:22618240

  7. Mortality after total hip replacement surgery

    PubMed Central

    Berstock, J. R.; Beswick, A. D.; Lenguerrand, E.; Whitehouse, M. R.; Blom, A. W.

    2014-01-01

    Total hip replacement causes a short-term increase in the risk of mortality. It is important to quantify this and to identify modifiable risk factors so that the risk of post-operative mortality can be minimised. We performed a systematic review and critical evaluation of the current literature on the topic. We identified 32 studies published over the last 10 years which provide either 30-day or 90-day mortality data. We estimate the pooled incidence of mortality during the first 30 and 90 days following hip replacement to be 0.30% (95% CI 0.22 to 0.38) and 0.65% (95% CI 0.50 to 0.81), respectively. We found strong evidence of a temporal trend towards reducing mortality rates despite increasingly co-morbid patients. The risk factors for early mortality most commonly identified are increasing age, male gender and co-morbid conditions, particularly cardiovascular disease. Cardiovascular complications appear to have overtaken fatal pulmonary emboli as the leading cause of death after hip replacement. Cite this article: Bone Joint Res 2014;3:175–82. PMID:24894596

  8. Experimental replacement of an obligate insect symbiont.

    PubMed

    Moran, Nancy A; Yun, Yueli

    2015-02-17

    Symbiosis, the close association of unrelated organisms, has been pivotal in biological diversification. In the obligate symbioses found in many insect hosts, organisms that were once independent are permanently and intimately associated, resulting in expanded ecological capabilities. The primary model for this kind of symbiosis is the association between the bacterium Buchnera and the pea aphid (Acyrthosiphon pisum). A longstanding obstacle to efforts to illuminate genetic changes underlying obligate symbioses has been the inability to experimentally disrupt and reconstitute symbiont-host partnerships. Our experiments show that Buchnera can be experimentally transferred between aphid matrilines and, furthermore, that Buchnera replacement has a massive effect on host fitness. Using a recipient pea aphid matriline containing Buchnera that are heat sensitive because of an allele eliminating the heat shock response of a small chaperone, we reduced native Buchnera through heat exposure and introduced a genetically distinct Buchnera from another matriline, achieving complete replacement and stable inheritance. This transfer disrupted 100 million years (∼ 1 billion generations) of continuous maternal transmission of Buchnera in its host aphids. Furthermore, aphids with the Buchnera replacement enjoyed a dramatic increase in heat tolerance, directly demonstrating a strong effect of symbiont genotype on host ecology.

  9. Experimental replacement of an obligate insect symbiont.

    PubMed

    Moran, Nancy A; Yun, Yueli

    2015-02-17

    Symbiosis, the close association of unrelated organisms, has been pivotal in biological diversification. In the obligate symbioses found in many insect hosts, organisms that were once independent are permanently and intimately associated, resulting in expanded ecological capabilities. The primary model for this kind of symbiosis is the association between the bacterium Buchnera and the pea aphid (Acyrthosiphon pisum). A longstanding obstacle to efforts to illuminate genetic changes underlying obligate symbioses has been the inability to experimentally disrupt and reconstitute symbiont-host partnerships. Our experiments show that Buchnera can be experimentally transferred between aphid matrilines and, furthermore, that Buchnera replacement has a massive effect on host fitness. Using a recipient pea aphid matriline containing Buchnera that are heat sensitive because of an allele eliminating the heat shock response of a small chaperone, we reduced native Buchnera through heat exposure and introduced a genetically distinct Buchnera from another matriline, achieving complete replacement and stable inheritance. This transfer disrupted 100 million years (∼ 1 billion generations) of continuous maternal transmission of Buchnera in its host aphids. Furthermore, aphids with the Buchnera replacement enjoyed a dramatic increase in heat tolerance, directly demonstrating a strong effect of symbiont genotype on host ecology. PMID:25561531

  10. 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.

  11. Macitentan (ACT-064992), a tissue-targeting endothelin receptor antagonist, enhances therapeutic efficacy of paclitaxel by modulating survival pathways in orthotopic models of metastatic human ovarian cancer.

    PubMed

    Kim, Sun-Jin; Kim, Jang Seong; Kim, Seung Wook; Brantley, Emily; Yun, Seok Joong; He, Junqin; Maya, Marva; Zhang, Fahao; Wu, Qiuyu; Lehembre, François; Regenass, Urs; Fidler, Isaiah J

    2011-02-01

    Potential treatments for ovarian cancers that have become resistant to standard chemotherapies include modulators of tumor cell survival, such as endothelin receptor (ETR) antagonist. We investigated the therapeutic efficacy of the dual ETR antagonist, macitentan, on human ovarian cancer cells, SKOV3ip1 and IGROV1, growing orthotopically in nude mice. Mice with established disease were treated with vehicle (control), paclitaxel (weekly, intraperitoneal injections), macitentan (daily oral administrations), or a combination of paclitaxel and macitentan. Treatment with paclitaxel decreased tumor weight and volume of ascites. Combination therapy with macitentan and paclitaxel reduced tumor incidence and further reduced tumor weight and volume of ascites when compared with paclitaxel alone. Macitentan alone occasionally reduced tumor weight but alone had no effect on tumor incidence or ascites. Immunohistochemical analyses revealed that treatment with macitentan and macitentan plus paclitaxel inhibited the phosphorylation of ETRs and suppressed the survival pathways of tumor cells by decreasing the levels of pVEGFR2, pAkt, and pMAPK. The dose of macitentan necessary for inhibition of phosphorylation correlated with the dose required to increase antitumor efficacy of paclitaxel. Treatment with macitentan enhanced the cytotoxicity mediated by paclitaxel as measured by the degree of apoptosis in tumor cells and tumor-associated endothelial cells. Collectively, these results show that administration of macitentan in combination with paclitaxel prevents the progression of ovarian cancer in the peritoneal cavity of nude mice in part by inhibiting survival pathways of both tumor cells and tumor-associated endothelial cells.

  12. 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.

  13. Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model.

    PubMed

    Parayath, Neha N; Nehoff, Hayley; Norton, Samuel E; Highton, Andrew J; Taurin, Sebastien; Kemp, Roslyn A; Greish, Khaled

    2016-01-01

    Oral administration of paclitaxel (PTX), a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid) (SMA). Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg) compared to the commercially available PTX formulation (PTX [Ebewe]). In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe). In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. PMID:27574427

  14. Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats

    PubMed Central

    Shevtsov, M. A.; Parr, M. A.; Ryzhov, V. A.; Zemtsova, E. G.; Arbenin, A. Yu; Ponomareva, A. N.; Smirnov, V. M.; Multhoff, G.

    2016-01-01

    Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues. PMID:27386761

  15. Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model

    PubMed Central

    Parayath, Neha N; Nehoff, Hayley; Norton, Samuel E; Highton, Andrew J; Taurin, Sebastien; Kemp, Roslyn A; Greish, Khaled

    2016-01-01

    Oral administration of paclitaxel (PTX), a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid) (SMA). Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg) compared to the commercially available PTX formulation (PTX [Ebewe]). In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe). In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. PMID:27574427

  16. Noninvasive Monitoring of mRFP1- and mCherry-Labeled Oncolytic Adenoviruses in an Orthotopic Breast Cancer Model by Spectral Imaging

    PubMed Central

    Borovjagin, Anton V.; McNally, Lacey R.; Wang, Minghui; Curiel, David T.; MacDougall, Mary J.; Zinn, Kurt R.

    2010-01-01

    Genetic capsid labeling of conditionally replicative adenoviruses (CRAds) with fluorescent tags offers a potentially more accurate monitoring of those virotherapy agents in vivo. The capsid of an infectivity-enhanced CRAd, Ad5/3, delta 24, was genetically labeled with monomeric red fluorescent protein 1 (mRFP1) or its advanced derivative, “mCherry,” to evaluate the utility of each red fluorescent reporter and the benefit of CRAd capsid labeling for noninvasive virus tracking in animal tumor models by a new spectral imaging approach. Either reporter was incorporated into the CRAd particles by genetic fusion to the viral capsid protein IX. Following intratumoral injection, localization and replication of each virus in orthotopic breast cancer xenografts were analyzed by spectral imaging and verified by quantitative polymerase chain reaction. Fluorescence in tumors increased up to 2,000-fold by day 4 and persisted for 5 to 7 weeks, showing oscillatory dynamics reflective of CRAd replication cycles. Capsid labeling in conjunction with spectral imaging thus enables direct visualization and quantification of CRAd particles in tumors prior to the reporter transgene expression. This allows for noninvasive control of CRAd delivery and distribution in tumors and facilitates quantitative assessment of viral replication. Although mCherry appeared to be superior to mRFP1 as an imaging tag, both reporters showed utility for CRAd imaging applications. PMID:20236604

  17. Pharmacokinetics of Gd(DO3A-Lys) and MR imaging studies in an orthotopic U87MG glioma tumor model.

    PubMed

    Chandrasekharan, Prashant; Yang, Chang-Tong; Nasrallah, Fatima Ali; Tay, Hui Chien; Chuang, Kai-Hsiang; Robins, Edward G

    2015-01-01

    Pharmacokinetics of Gd(DO3A-Lys), a macrocyclic gadolinium-based magnetic resonance imaging (MRI) contrast agent functionalized with a lysine derivative, was studied in Wistar rats. Kinetic data were fitted using a two-compartment model and revealed Gd(DO3A-Lys) to have a distribution half-life, t1/2 (α), of 1.3 min, an elimination half-life, t1/2 (β), of 24.9 min and a large volume of distribution, VD , of 0.49 L/kg indicative of the agent being able to rapidly distribute into tissues and organs. Contrast-enhanced magnetic resonance angiography (CE-MRA) in an orthotopic U87MG glioma mouse model demonstrated considerable enhancement of both the tumor and surrounding vasculature after intravenous administration of Gd(DO3A-Lys). Applying dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the glioma of different sizes further showed distinct uptake characteristics and patterns of enhancement, which suggests the potential for differentiating changes at different stages of tumor growth. Our results indicate that Gd(DO3A-Lys) could be a promising candidate for glioma MR imaging. PMID:25612157

  18. 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.

  19. Orthotopic liver transplantation from a living-related donor in an infant with a peroxisome biogenesis defect of the infantile Refsum disease type.

    PubMed

    Van Maldergem, L; Moser, A B; Vincent, M-F; Roland, D; Reding, R; Otte, J-B; Wanders, R J; Sokal, E

    2005-01-01

    Peroxisomal biogenesis defects include a number of severe neurodevelopmental disorders, among which infantile Refsum disease (IRD) occupies the mildest end of the spectrum. Although high docosahexaenoic acid (DHA) and low phytanic acid diets can correct some of the biochemical defects, they have not consistently altered the progressive course of the disease. We carried out orthotopic liver transplantation (OLT) in a mildly symptomatic 6-month-old infant who was a sibling of a severely neurologically impaired older sister. After transplantation the clinical course of this young child appeared much improved by comparison to her older sister. She walked alone at 4 years, had acceptable social interaction and had a noticeable recovery of audition. After transplantation her biochemical parameters were significantly improved: phytanic acid and very long-chain fatty acid (VLCFA) serum concentrations decreased. Abnormal bile acids disappeared from plasma. Although the OLT did not result in a cure of the disorder, the clinical and biochemical results suggest that OLT should be considered in mildly symptomatic patients.

  20. Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy

    PubMed Central

    Chen, Yijie; Wang, Xinran; Liu, Ting; Zhang, Ding Sheng-zi; Wang, Yunfei; Gu, Hongchen; Di, Wen

    2015-01-01

    Therapeutic antiangiogenesis strategies have demonstrated significant antitumor efficacy in ovarian cancer. Recently, RNA interference (RNAi) has come to be regarded as a promising technology for treatment of disease, especially cancer. In this study, vascular endothelial growth factor (VEGF)-small interfering RNA (siRNA) was encapsulated into a magnetic mesoporous silica nanoparticle (M-MSN)-based, polyethylenimine (PEI)-capped, polyethylene glycol (PEG)-grafted, fusogenic peptide (KALA)-functionalized siRNA delivery system, termed M-MSN_VEGF siRNA@PEI-PEG-KALA, which showed significant effectiveness with regard to VEGF gene silencing in vitro and in vivo. The prepared siRNA delivery system readily exhibited cellular internalization and ease of endosomal escape, resulting in excellent RNAi efficacy without associated cytotoxicity in SKOV3 cells. In in vivo experiments, notable retardation of tumor growth was observed in orthotopic ovarian tumor-bearing mice, which was attributed to significant inhibition of angiogenesis by systemic administration of this nanocarrier. No obvious toxic drug responses were detected in major organs. Further, the magnetic core of M-MSN_VEGF siRNA@PEI-PEG-KALA proved capable of probing the site and size of the ovarian cancer in mice on magnetic resonance imaging. Collectively, the results demonstrate that an M-MSN-based delivery system has potential to serve as a carrier of siRNA therapeutics in ovarian cancer. PMID:25848273

  1. Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model

    PubMed Central

    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. PMID:26855572

  2. Gas gangrene caused by clostridium perfringens involving the liver, spleen, and heart in a man 20 years after an orthotopic liver transplant: a case report.

    PubMed

    Kitterer, Daniel; Braun, Niko; Jehs, Margit C; Schulte, Bernhard; Alscher, M Dominik; Latus, Joerg

    2014-04-01

    Despite advances in immunosuppression and liver transplant in the past, mortality and morbidity caused by infections remain major problems. We present a 71-year-old man who was admitted to our internal intensive care unit with septicemia. Upon admission, he had poorly localized epigastric pain and fever of 2 days ' duration. Twenty years earlier, he had undergone an orthotopic liver transplant. Testing revealed a high C-reactive protein level, elevated liver enzymes, and an acute kidney injury. A computer tomography scan showed 2 circular, non--rim-enhancing, totally emphysematous intrahepatic lesions. Additionally, gas could be seen in the portal veins mainly, as well as in the biliary system, in the right auricle, and the splenic veins. To the best of our knowledge, he showed no malignant lesion or predisposing trauma. Empirically, treatment with broad-spectrum antibiotics was begun, and the patient was transferred to the operating suite. When surgery began, blood cultures revealed the presence of gram-positive bacilli, which were identified as Clostridium perfringens. Seven hours after the surgery, the patient developed asystole and died. In septic patients presenting with severe hemolysis, Clostridium perfringens infection must be considered in the absence of a malignant lesion or a predisposing trauma; a previous episode of gastroenteritis might be a predisposing trauma by impairing the barrier of the intestinal flora, leading to Clostridium perfringens infection.

  3. Protective effect of a protein-bound polysaccharide, PSK, on CLP-induced sepsis in mice transplanted orthotopically with colon tumor.

    PubMed

    Ohmura, Yoshio; Matsunaga, Kenichi; Suzuki, Tatsuo

    2006-01-01

    We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against sepsis induced by cecal ligation and puncture (CLP). (a) In BALB/c mice that had received intracecal transplantation of colon 26 (C26) tumor, CLP with a 21-gauge needle significantly shortened the survival time, compared with that of non-tumor-bearing mice. Oral administration of PSK to such mice resulted in a significant prolongation of the survival time and increase of the survival rates. The effects were dependent on the timing of PSK administration and the dose. (b) CLP significantly increased the IL-10 level in serum, the IL-10 gene expression by spleen cells, the number of IL-10-producing CD4-positive T cells, and the productivity of IL-10 by spleen of tumor-bearing mice compared with that of non-tumor-bearing mice. PSK administration to such mice suppressed the increase. Further, PSK prevented the reduction of gene expression of IFN-gamma and the number of IFN-gamma-producing CD4-positive T cells and IFN-gamma productivity by spleen cells of tumor-bearing CLP-treated mice. (c) Treatment with anti-IFN-gamma monoclonal antibody before CLP significantly reduced the effects of PSK. These findings suggest that the protective effect of PSK on the CLP-induced sepsis in mice transplanted orthotopically with C26 tumor is possibly mediated by suppression of IL-10 and promotion of IFN-gamma. PMID:16369184

  4. Successful orthotopic liver transplantation and delayed delivery of a healthy newborn in a woman with fulminant hepatic failure during the second trimester of pregnancy.

    PubMed

    Mendizabal, Manuel; Rowe, Carlos; Piñero, Federico; Gonzalez-Campaña, Ariel; Fauda, Martín; Tomás Arufe, Diego; Pía Raffa, María; Barreiro, Mariano; Keller, Rodolfo; Cacheiro, Fernando; Beruti, Ernesto; Andriani, Oscar; Oscar Silva, Marcelo; Podestá, Luis Gustavo

    2014-01-01

    Severe liver dysfunction during pregnancy implies a serious risk for both mother and fetus, and represents a technical and ethical challenge for treating physicians. We report a case of a previously healthy 32-year old woman who was admitted to our hospital with idiopathic fulminant hepatic failure and underwent successful orthotopic liver transplantation (OLT) at gestation week 21. Patient's and fetus' immediate postoperative course were relatively uneventful until week six after OLT, when the mother developed oligohydramnios and preeclampsia. At pregnancy week 27, after inducing baby's lung maturation, a cesarean section was performed with the delivery of an otherwise healthy girl. After 3 years of follow-up, mother and child are leading normal lives with no complications related either to pregnancy or to OLT. We describe the case of a successful emergency liver transplant in a woman during the second trimester of pregnancy, demonstrating that OLT can be a viable option to preserve the life of the mother and an otherwise unviable fetus. Intrauterine baby's growths until the attainment of a viable gestational age was feasible despite the mother's fulminant hepatic failure and liver transplant surgery.

  5. Tomography of epidermal growth factor receptor binding to fluorescent Affibody in vivo studied with magnetic resonance guided fluorescence recovery in varying orthotopic glioma sizes

    PubMed Central

    Holt, Robert W.; Demers, Jennifer-Lynn H.; Sexton, Kristian J.; Gunn, Jason R.; Davis, Scott C.; Samkoe, Kimberley S.; Pogue, Brian W.

    2015-01-01

    Abstract. 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. PMID:25652703

  6. Tomography of epidermal growth factor receptor binding to fluorescent Affibody in vivo studied with magnetic resonance guided fluorescence recovery in varying orthotopic glioma sizes.

    PubMed

    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. PMID:25652703

  7. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model.

    PubMed

    Benedetti, Elisabetta; Antonosante, Andrea; d'Angelo, Michele; Cristiano, Loredana; Galzio, Renato; Destouches, Damien; Florio, Tiziana Marilena; Dhez, Anne Chloé; Astarita, Carlo; Cinque, Benedetta; Fidoamore, Alessia; Rosati, Floriana; Cifone, Maria Grazia; Ippoliti, Rodolfo; Giordano, Antonio; Courty, José; Cimini, Annamaria

    2015-12-01

    Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma.

  8. Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success

    PubMed Central

    Lin, Xue; Li, Wenjun; Lai, Jiaming; Okazaki, Mikio; Sugimoto, Seiichiro; Yamamoto, Sumiharu; Wang, Xingan; Gelman, Andrew E.; Kreisel, Daniel

    2012-01-01

    It has been 5 years since our team reported the first successful model of orthotopic single lung transplantation in the mouse. There has been great demand for this technique due to the obvious experimental advantages the mouse offers over other large and small animal models of lung transplantation. These include the availability of mouse-specific reagents as well as knockout and transgenic technology. Our laboratory has utilized this mouse model to study both immunological and non-immunological mechanisms of lung transplant physiology while others have focused on models of chronic rejection. It is surprising that despite our initial publication in 2007 only few other laboratories have published data using this model. This is likely due to the technical complexity of the surgical technique and perioperative complications, which can limit recipient survival. As two of the authors (XL and WL) have a combined experience of over 2500 left and right single lung transplants, this review will summarize their experience and delineate tips and tricks necessary for successful transplantation. We will also describe technical advances made since the original description of the model. PMID:22754663

  9. Simultaneous Inhibition of EGFR, VEGFR and PDGFR Signaling Combined with Gemcitabine Produces Therapy of Human Pancreatic Carcinoma and Prolongs Survival in an Orthotopic Nude Mouse Model

    PubMed Central

    Yokoi, Kenji; Sasaki, Takamitsu; Bucana, Corazon D.; Fan, Dominic; Baker, Cheryl H.; Kitadai, Yasuhiko; Kuwai, Toshio; Abbruzzese, James L.; Fidler, Isaiah J.

    2006-01-01

    Although gemcitabine has been approved as the first-line chemotherapeutic reagent for pancreatic cancer, its response rate is low and average survival duration is still only marginal. Because epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR) modulate tumor progression, we hypothesized that inhibition of phosphorylation of all three on tumor cells, tumor-associated endothelial cells, and stroma cells would improve the treatment efficacy of gemcitabine in an orthotopic pancreatic tumor model in nude mice and prolong survival. We implanted L3.6pl, a human pancreatic cancer cell, in the pancreas of nude mice. We found that tumor-associated endothelial cells in this model highly expressed phosphorylated EGFR, VEGFR, and PDGFR. Oral administration of AEE788, a dual tyrosine kinase inhibitor against EGFR and VEGFR, decreased phosphorylation of EGFR and VEGFR. PDGFR phosphorylation was inhibited by STI571. Although intraperitoneal (i.p.) injection of gemcitabine did not inhibit tumor growth, its combination with AEE788 and STI571 produced >80% inhibition of tumor growth and prolonged survival in parallel with increases in number of tumor cells and tumor-associated endothelial cell apoptosis, decreased microvascular density, decreased proliferation rate, and prolonged survival. STI571 treatment also decreased pericyte coverage on tumor-associated endothelial cells. Thus, inhibiting phosphorylation of EGFR, VEGFR, and PDGFR in combination with gemcitabine enhanced the efficacy of gemcitabine, resulting in inhibition of experimental human pancreatic cancer growth and significant prolongation of survival. PMID:16288027

  10. Label-Free Delineation of Brain Tumors by Coherent Anti-Stokes Raman Scattering Microscopy in an Orthotopic Mouse Model and Human Glioblastoma

    PubMed Central

    Tamosaityte, Sandra; Leipnitz, Elke; Geiger, Kathrin D.; Schackert, Gabriele; Koch, Edmund; Steiner, Gerald; Kirsch, Matthias

    2014-01-01

    Background Coherent anti-Stokes Raman scattering (CARS) microscopy provides fine resolution imaging and displays morphochemical properties of unstained tissue. Here, we evaluated this technique to delineate and identify brain tumors. Methods Different human tumors (glioblastoma, brain metastases of melanoma and breast cancer) were induced in an orthotopic mouse model. Cryosections were investigated by CARS imaging tuned to probe C-H molecular vibrations, thereby addressing the lipid content of the sample. Raman microspectroscopy was used as reference. Histopathology provided information about the tumor's localization, cell proliferation and vascularization. Results The morphochemical contrast of CARS images enabled identifying brain tumors irrespective of the tumor type and properties: All tumors were characterized by a lower CARS signal intensity than the normal parenchyma. On this basis, tumor borders and infiltrations could be identified with cellular resolution. Quantitative analysis revealed that the tumor-related reduction of CARS signal intensity was more pronounced in glioblastoma than in metastases. Raman spectroscopy enabled relating the CARS intensity variation to the decline of total lipid content in the tumors. The analysis of the immunohistochemical stainings revealed no correlation between tumor-induced cytological changes and the extent of CARS signal intensity reductions. The results were confirmed on samples of human glioblastoma. Conclusions CARS imaging enables label-free, rapid and objective identification of primary and secondary brain tumors. Therefore, it is a potential tool for diagnostic neuropathology as well as for intraoperative tumor delineation. PMID:25198698

  11. miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

    PubMed

    Zou, Yongkang; Li, Jianwei; Chen, Zhiyu; Li, Xiaowu; Zheng, Shuguo; Yi, Dong; Zhong, Ai; Chen, Jian

    2015-06-01

    We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

  12. 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.

  13. Validation of a femoral critical size defect model for orthotopic evaluation of bone healing: a biomechanical, veterinary and trauma surgical perspective.

    PubMed

    Drosse, Inga; Volkmer, Elias; Seitz, Sebastian; Seitz, Hermann; Penzkofer, Rainer; Zahn, Klaus; Matis, Ulrike; Mutschler, Wolf; Augat, Peter; Schieker, Matthias

    2008-03-01

    Numerous in vivo studies have been conducted to investigate bone regeneration in orthotopic defect models, but a reliably standardized critical-size defect (CSD) model in small animals is still lacking in tissue-engineering research. Utilizing the expertise of trauma surgeons, veterinary surgeons, and engineers, we evaluated the optimal fixation strategy for in vivo application in terms of surgical suitability and conducted biomechanical studies for 3 fixation devices. Fixation strategies were an external fixation device made of polymethylmethacrylate, widely used in animal care; a self-constructed external clamp-fixation device, designed and manufactured using rapid prototyping techniques; and commercially available 1.2-mm titanium plates used in hand surgery. The CSD was 6 mm in size. Biomechanical testing included compression, 4-point bending, and torsion tests. The surgical procedure was optimized in vitro and validated in a clinical setting in athymic rats in vivo. Despite differences in the results of the biomechanical tests, all fixation devices tested proved suitable for the intended purpose. In conclusion, the evaluated model for stabilizing a CSD in a rat's femur can reliably be used for standardized bone regeneration studies in small animals.

  14. Renal function after elective total hip replacement.

    PubMed

    Perregaard, Helene; Damholt, Mette B; Solgaard, Søren; Petersen, Morten B

    2016-06-01

    Background and purpose - Acute kidney injury (AKI) is associated with increased short-term and long-term mortality in intensive care populations and in several surgical specialties, but there are very few data concerning orthopedic populations. We have studied the incidence of AKI and the prevalence of chronic kidney disease (CKD) in an elective population of orthopedic patients undergoing primary total hip replacement, hypothesizing that chronic kidney disease predisposes to AKI. Patients and methods - This was a single-center, population-based, retrospective, registry-based cohort study involving all primary elective total hip replacements performed from January 2003 through December 2012. Patient demographics and creatinine values were registered. We evaluated the presence of CKD and AKI according to the international guidelines for kidney disease (KDIGO Acute Kidney Injury Workgroup 2013 ). Results - 3,416 patients were included (2,064 females (60%)). AKI (according to KDIGO criteria) was seen in 75 patients (2.2%, 95% CI: 1.7-2.7) in the course of primary total hip replacement. Of these, 26 had pre-existing CKD of class 3-5. Pre-existing CKD of class 3-5, indicating moderately to severely reduced kidney function, was seen in 374 individuals (11%). Interpretation - Development of acute kidney injury appears to be a substantial problem compared to other complications related to elective total hip arthroplasty, i.e. luxation and infection. Patients with pre-existing chronic kidney disease may be especially vulnerable. The clinical impact of acute kidney injury in an elective orthopedic population remains to be elucidated. PMID:26937782

  15. Can electronic stability control replace studded tyres?

    PubMed

    Elvik, Rune

    2015-12-01

    Based on recent studies, this paper examines whether an increased use of electronic stability control can replace studded tyres. A re-analysis of a study that evaluated the effects on accidents of changes in the use of studded tyres in major cities in Norway is presented. It is found that if all cars have electronic stability control, the use of studded tyres can be reduced to about 15 percent before any increase in the number of accidents occurs. Even if studded tyres were eliminated entirely, any increase in the number of accidents is likely to be considerably smaller than it would have been if electronic stability control had never been invented.

  16. Trials and Tribulations with VH Replacement.

    PubMed

    Meng, Wenzhao; Jayaraman, Sahana; Zhang, Bochao; Schwartz, Gregory W; Daber, Robert D; Hershberg, Uri; Garfall, Alfred L; Carlson, Christopher S; Luning Prak, Eline T

    2014-01-01

    VH replacement (VHR) is a type of antibody gene rearrangement in which an upstream heavy chain variable gene segment (VH) invades a pre-existing rearrangement (VDJ). In this Hypothesis and Theory article, we begin by reviewing the mechanism of VHR, its developmental timing and its potential biological consequences. Then we explore the hypothesis that specific sequence motifs called footprints reflect VHR versus other processes. We provide a compilation of footprint sequences from different regions of the antibody heavy chain, and include data from the literature and from a high throughput sequencing experiment to evaluate the significance of footprint sequences. We conclude by discussing the difficulties of attributing footprints to VHR.

  17. Alternatives to testosterone replacement: testosterone restoration

    PubMed Central

    McCullough, Andrew

    2015-01-01

    The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH. PMID:25578932

  18. The befores and afters of molecular replacement

    PubMed Central

    Dodson, Eleanor

    2008-01-01

    This review addresses the essential questions to consider when attempting to phase a new crystal structure using molecular replacement. Sequence matching can suggest whether there is a suitable three-dimensional model available, but it is also important to analyse the model in order to find its likely oligomeric state and to establish whether there are likely to be domain movements. Once a solution has been found it must be refined, which can be challenging for low-homology models. There is a detailed discussion of structures used as examples for CCP4 tutorials. PMID:18094463

  19. Soft tissue balancing in total shoulder replacement.

    PubMed

    Mueller, Maike; Hoy, Gregory

    2014-03-01

    Total shoulder arthroplasty is now capable of recreating near anatomic reproduction of native bony shoulder anatomy, but the function and longevity of anatomic shoulder replacement is dependent on a competent soft tissue envelope and adequate motoring of all musculo-tendinous units about the shoulder. Balancing the soft tissues requires understanding of the anatomy and pathology, as well as technical skills. The advent of reverse shoulder biomechanics has brought with it special requirements of understanding of the soft tissue elements still left in the shoulder despite major rotator cuff deficiency.

  20. Aortic Annular Enlargement during Aortic Valve Replacement

    PubMed Central

    Dumani, Selman; Likaj, Ermal; Dibra, Laureta; Llazo, Stavri; Refatllari, Ali

    2016-01-01

    In the surgery of aortic valve replacement is always attempted, as much as possible, to implant the larger prosthesis with the mains goals to enhance the potential benefits, to minimise transvalvular gradient, decrease left ventricular size and avoid the phenomenon of patient-prosthesis mismatch. Implantation of an ideal prosthesis often it is not possible, due to a small aortic annulus. A variety of aortic annulus enlargement techniques is reported to avoid patient-prosthesis mismatch. We present the case that has submitted four three times open heart surgery. We used Manouguian technique to enlarge aortic anulus with excellent results during the fourth time of surgery. PMID:27703574

  1. Current status of valve replacement in children.

    PubMed

    Schaff, H V; Danielson, G K

    1986-01-01

    Management of valve diseases in children demands an eclectic approach by the surgeon. Whenever possible, valve function should be restored by repair rather than prosthetic replacement. Recent evidence firmly demonstrates that there are accelerated calcification and degeneration of porcine heterografts in children, especially in the aortic and mitral positions. For this reason, we reserve the use of heterograft prostheses for the right atrioventricular position and for conduits from the right ventricle to the pulmonary artery. Such patients are observed carefully for signs of valve degeneration. Long-term followup of the Starr-Edwards prosthesis in children demonstrates excellent durability and a thromboembolic rate that is equal to or lower than that found in adult patients. Hemodynamic properties of the Starr-Edwards valve are adequate even in the smallest size used in infants and have allowed children to reach early adolescence at which time valve re-replacement with an adult-sized prosthesis is possible. Intermediate-term experience with the Bjork-Shiley valve in children has also been favorable. At present we continue to use systemic anticoagulation with warfarin in all children with mechanical prostheses. PMID:3742534

  2. Limitations to fluid replacement during exercise.

    PubMed

    Maughan, R J; Leiper, J B

    1999-04-01

    Fluid replacement during exercise is essential for endurance exercise performance and reducing the risk of heat illness. Fluids supply water, which ameliorates dehydration, and also substrate for the working muscles. Absorption of water and nutrients occurs in the upper part of the small intestine, and replacement may be limited by the rate at which fluid is emptied from the stomach or absorbed in the intestine. Gastric emptying of liquids is influenced primarily by the volume of fluid in the stomach and by its energy density. Increasing the volume will speed emptying, but increasing the nutrient content will slow emptying. Osmolality, temperature, and pH of drinks, as well as exercise intensity, are of minor importance. Intestinal water absorption is a passive process: water follows osmotic gradients but will also follow the active absorption of nutrients, especially glucose, which is actively co-transported with sodium. Water transport is maximised by the presence in the intestine of hypotonic solutions of glucose and sodium. Hypertonic solutions promote net water secretion into the intestinal lumen, resulting in a temporary net loss of water from the body. The amount of fluid ingested by athletes is normally much less than can be tolerated, therefore issues such as palatability and practising drinking during training are important.

  3. Recombinant Enzyme Replacement Therapy in Hypophosphatasia.

    PubMed

    Hofmann, Christine; Jakob, Franz; Seefried, Lothar; Mentrup, Birgit; Graser, Stephanie; Plotkin, Horacio; Girschick, Hermann J; Liese, Johannes

    2015-01-01

    Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with involvement of different organs, including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The exact metabolic mechanisms of the effects of TNAP deficiency in different tissues are not understood in detail. There is no approved specific treatment for HPP; therefore symptomatic treatment in order to improve the clinical features is of major interest. Enzyme replacement therapy (ERT) is a relatively new type of treatment based on the principle of administering a medical treatment replacing a defective or absent enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has been reported to be efficient in ten severely affected patients and improved survival of life threatening forms. These results are very promising especially with regard to the skeletal phenotype but it is unclear whether ERT also has beneficial effects for craniosynostosis and in other affected tissues in HPP such as brain and kidney. Long-term data are not yet available and further systematic clinical trials are needed. It is also necessary to establish therapeutic approaches to help patients who are affected by less severe forms of HPP but also suffer from a significant reduction in quality of life. Further basic research on TNAP function and role in different tissues and on its physiological substrates is critical to gain a better insight in the pathogenesis in HPP. This and further experiences in new therapeutic strategies may improve the prognosis and quality of life of patients with all forms of HPP.

  4. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    PubMed Central

    Underbjerg, Line; Sikjaer, Tanja

    2015-01-01

    Hypoparathyroidism (HypoPT) is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH). Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL) and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84)) as well as therapy with the N-terminal PTH fragment (rhPTH(1-34)) have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy. PMID:26394728

  5. Limitations to fluid replacement during exercise.

    PubMed

    Maughan, R J; Leiper, J B

    1999-04-01

    Fluid replacement during exercise is essential for endurance exercise performance and reducing the risk of heat illness. Fluids supply water, which ameliorates dehydration, and also substrate for the working muscles. Absorption of water and nutrients occurs in the upper part of the small intestine, and replacement may be limited by the rate at which fluid is emptied from the stomach or absorbed in the intestine. Gastric emptying of liquids is influenced primarily by the volume of fluid in the stomach and by its energy density. Increasing the volume will speed emptying, but increasing the nutrient content will slow emptying. Osmolality, temperature, and pH of drinks, as well as exercise intensity, are of minor importance. Intestinal water absorption is a passive process: water follows osmotic gradients but will also follow the active absorption of nutrients, especially glucose, which is actively co-transported with sodium. Water transport is maximised by the presence in the intestine of hypotonic solutions of glucose and sodium. Hypertonic solutions promote net water secretion into the intestinal lumen, resulting in a temporary net loss of water from the body. The amount of fluid ingested by athletes is normally much less than can be tolerated, therefore issues such as palatability and practising drinking during training are important. PMID:10198143

  6. Meniscus tear surgery and meniscus replacement

    PubMed Central

    Vaquero, Javier; Forriol, Francisco

    2016-01-01

    Summary Objective the menisci are easily injured and difficult to repair. The aim of this study was to analyze the current state of meniscal surgery aimed at preserving morphology and conserving the biomechanics of the knee to prevent joint degeneration. Methodology a search of the electronic medical literature database Medline was conducted, from http://www.ncbi.nlm.nih.gov/pubmed. The search was not limited by language. Candidate articles were identified by searching for those that included the keywords meniscus, surgery, suture, implant, allograft. The limits were included for clinical research and clinical trials. Basic research was not included. The studies selected were evaluated and classified in three different categories: basic science, reconstruction (suture and meniscectomy) and implants (scaffolds and allograft). Results the consequences of meniscectomy performed at a young age can lead to a joint cartilage degeneration twenty years later. There are few surgical options for the repair of meniscal injuries in order both to preserve the meniscus and to ensure the long term survival of the knee joint, meniscectomy, repair, suturing the tear, or reconstruction, when a meniscal allograft or synthetic substitute is used to replace the meniscus, but the biomechanical properties of the native meniscus are not reproduced entirely by the scaffolds that exist today. Conclusion therapies that successfully repair or replace the meniscus are therefore likely to prevent or delay osteoarthritis progression. PMID:27331034

  7. New replacement name Kuznetsoviella (Ostracoda): a correction.

    PubMed

    Doweld, Alexander B

    2016-01-01

    Recently it was found (Doweld 2016) that the generic name Aenigma Kuznetsova (1957: 68; type species A. jucunda Kuznetsova, by original designation) of fossil Ostracoda from the Lower Cretaceous (Barremian) of Tegchaj, North-Eastern Azerbaijan, former USSR (Transcaucasia), is already preoccupied by a marine gastropod molluscan generic name Aenigma Newman (1836: 499), which is in active current use in zoology (Coleoptera: Carabidae), along with a few other known homonyms, Aenigma Amsel (1956: 288) [Lepidoptera], Aenigma Koch (in Martini & Chemnitz 1846: 1, unpaginated) [Mollusca], Aenigma Karsch (1878: 825) [Arachnida], Aenigma Strecker (1876: 122) [Lepidoptera]. Therefore, a new replacement name was proposed, Kuznetsovia Doweld (2016: 68). However, it was overlooked that this generic name is already preoccupied by Kuznetsovia Kammerer (2006: 269) [Arthropoda], escaped from Nomenclator Zoologicus and Zoobank. In this connection, to resolve unexpected homonymy with an arthropod generic name, in accordance with article 60 of the International Code of Zoological Nomenclature (1999), a new replacement name is proposed for the fossil Ostracoda genus:. PMID:27470720

  8. Aortic valve replacement with combined myocardial revascularisation.

    PubMed Central

    Jones, M; Schofield, P M; Brooks, N H; Dark, J F; Moussalli, H; Deiraniya, A K; Lawson, R A; Rahman, A N

    1989-01-01

    Early and late outcome was studied in 630 patients who underwent aortic valve replacement between 1974 and 1982. Group 1 (506 patients) did not have important coronary artery disease, group 2 (69 patients) had coronary artery disease and underwent coronary artery bypass grafting, and group 3 (55 patients) had coronary artery disease but did not undergo myocardial revascularisation. Early mortality (within 30 days of operation) was significantly lower for group 1 (6%) than for group 2 (13%) and for group 3 (16%). Operative mortality in all three groups was lower in patients operated on more recently. The three year survival of patients in group 1 (83%) was significantly higher than that of patients in group 3 (62%) but not than that of patients in group 2 (76%). The findings of this study suggest that the presence of coronary artery disease increases the risk of aortic valve replacement whether or not coronary artery grafting is performed. Myocardial revascularisation, however, seems to return patients with aortic valve and coronary artery disease to a survival curve similar to that of patients with isolated aortic valve disease. PMID:2788003

  9. Advances in Transcatheter Aortic Valve Replacement

    PubMed Central

    Kleiman, Neal S.; Reardon, Michael J.

    2016-01-01

    Transcatheter aortic valve replacement (TAVR) is becoming widely used for the treatment of symptomatic severe aortic stenosis in patients with high surgical risk. Data from The PARTNER Trial (Placement of AoRtic TraNscathetER Valves) and the Medtronic CoreValve® U.S. Pivotal Investigational Device Exemption trial indicate that survival for extreme-risk patients is superior to best medical therapy and equivalent or superior to surgical aortic valve replacement (SAVR), although long-term durability remains unknown. Paravalvular leak remains higher in TAVR than SAVR, as does permanent pacemaker implantation in self-expanding valves. New-generation valves are addressing these issues, especially for paravalvular leak. There is strong evidence that TAVR is appropriate for both extreme-risk and high-risk patients with symptomatic severe aortic stenosis, and the continued development of new valves are making implantation more reliable. This review discusses the studies supporting the use of TAVR and explores current advances in the field. PMID:27127560

  10. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone.

    PubMed

    Rejnmark, Lars; Underbjerg, Line; Sikjaer, Tanja

    2015-12-01

    Hypoparathyroidism (HypoPT) is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH). Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL) and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84)) as well as therapy with the N-terminal PTH fragment (rhPTH(1-34)) have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy. PMID:26394728

  11. Toward replacement fertility in Egypt and Tunisia.

    PubMed

    Eltigani, Eltigani E

    2009-09-01

    Egypt and Tunisia began their fertility transition at almost identical fertility levels and at roughly the same time period, yet the difference in the pace of decline has been such that the total fertility rate (TFR) in Tunisia reached replacement level by the year 2001, whereas the TFR in Egypt remains above three live births per woman. This article draws on the secondary literature and on several nationally representative surveys from the two countries between 1978 and 2005 to provide empirical evidence of the difference in the pace of fertility decline and to analyze the determinants of the differential. Findings include (a) variation across the two countries in the consistency of fertility decline among the segments of the population leading the transition; (b) that the success of each country's family planning program was influenced by the role of political leaders and the extent of the program's integration within socioeconomic development objectives; (c) that the impact of contraception on TFR decline became an important factor in the mid-1980s; and (d) that the greatest determinant of the discrepancy in the pace of fertility decline is the disparity in age at marriage, which rose more significantly in Tunisia than in Egypt. The latter finding indicates that reaching replacement fertility in Egypt hinges primarily on further declines in marital fertility, resulting from reduction of wanted fertility and from an expansion of family planning program coverage and improved efficiency of service delivery and use.

  12. Transdermal testosterone replacement therapy in men

    PubMed Central

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  13. Prospective evaluation of Foley catheter as a replacement gastrostomy tube.

    PubMed

    Kadakia, S C; Cassaday, M; Shaffer, R T

    1992-11-01

    Percutaneous endoscopic gastrostomy provides a nonsurgical alternative to enteral feeding. However, the percutaneous endoscopic gastrostomy tube may deteriorate, malfunction, or be accidentally expelled from the stomach, requiring replacement. This prospective study was performed to evaluate the use of an all silicone Foley catheter (Foley) as a replacement feeding gastrostomy in 28 patients requiring replacement gastrostomy. A plastic ring and a retention disc were always placed over the Foley prior to replacement. Foley functioned well without replacement in 19 (68%) patients for a mean of 167 days. It needed to be replaced in nine (32%) patients due to malfunction after a mean of 138 days. Lack of migration of Foley was the most striking finding of our study, in contrast to case reports in the literature. These data suggest that Foley can be safely used as replacement gastrostomy tube. A randomized controlled trial comparing the Foley catheter as a replacement tube with other commercially available devices is needed.

  14. The effect of fat replacers on batter and cake properties.

    PubMed

    Psimouli, Vassiliki; Oreopoulou, Vassiliki

    2013-10-01

    Fat was replaced at 35% to 100% in cakes by maltodextrin (dextrose equivalent = 3), inulin (high performance and granulated), oligofructose, citrus pectin, and microparticulated protein. Fat replacement by 35% did not induce significant differences in general. Above 65% fat replacement resulted in statistically significant (P < 0.05) decreased viscosity (except for pectin) that was followed by statistically significant decrease in air incorporation and broader bubble size distribution. The starch gelatinization temperature showed a statistically significant increase when fat was replaced by fructose oligosaccharides. The cakes presented statistically significant increase of hardness, elasticity, and decrease of volume development as fat replacement increased above 65%. Also cakes with increased fat replacement received lower scores on taste and flavor, whereas at total fat replacement they were evaluated as not acceptable. Nevertheless, at 65% fat replacement, the samples presented acceptable textural, physical, and sensorial attributes.

  15. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    MedlinePlus

    ... 1999 Spotlight on Research 2014 February 2014 (historical) Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder Replacing a protein that is crucial to ensuring that the skin’s ...

  16. Efficient targeting and tumor retardation effect of pancreatic adenocarcinoma up-regulated factor (PAUF)-specific RNA replacement in pancreatic cancer mouse model.

    PubMed

    Kim, Yun-Hee; Moon, Ju Young; Kim, Eun-Ok; Lee, Sang-Jin; Kang, Se Hun; Kim, Seok Ki; Heo, Kyun; Lee, Yusun; Kim, Hana; Kim, Kyung-Tae; Kim, Daehong; Song, Min Sun; Lee, Seoung-Wook; Lee, Yangsoon; Koh, Sang Seok; Kim, In-Hoo

    2014-03-28

    The soluble protein pancreatic adenocarcinoma up-regulated factor (PAUF) plays an important role in pancreatic tumor progression and has begun to attract attention as a therapeutic target for pancreatic cancer. We herein present PAUF RNA-targeting gene therapy strategies with both targeting and therapeutic function using trans-splicing ribozyme (TSR) in pancreatic cancer. We developed adenoviral PAUF-targeting TSR (Rz) containing a PAUF-specific internal guide sequence (IGS) determined by library screening. This Rz harbors suicide gene, herpes simplex virus thymidine kinase (HSV-tk) or firefly luciferase (Luc) as a transgene for 3' exon replacement of PAUF RNAs. Ad-Rz-TK, Rz harboring the HSV-tk, showed significant inhibition of tumor growth in vivo as well as PAUF-dependent cell death in vitro via a successful trans-splicing reaction. Selective induction of Rz-controlled transgene in PAUF-expressing pancreatic cancer was confirmed through noninvasive in vivo imaging; a luminescence signal from Rz harboring Luc (Ad-Rz-Luc) was detectable only in pancreatic tumor sites, not in normal mice. In addition, a [(125)I] FIAU signal reflecting thymidine kinase expression through SPECT and ex vivo biodistribution was co-localized with the tumor sites when we treated with Ad-Rz-TK in orthotopic xenograft model. Taken together, these results imply that PAUF-targeting TSR can contribute to successful targeted gene therapy for pancreatic cancer.

  17. 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...

  18. 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...

  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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 16 CFR 501.3 - Replacement bags for vacuum cleaners.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Replacement bags for vacuum cleaners. 501.3... REQUIREMENTS AND PROHIBITIONS UNDER PART 500 § 501.3 Replacement bags for vacuum cleaners. Replacement bags for vacuum cleaners, packaged and labeled for retail sale are exempt from the requirements of § 500.15a...

  7. 16 CFR 501.3 - Replacement bags for vacuum cleaners.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Replacement bags for vacuum cleaners. 501.3... REQUIREMENTS AND PROHIBITIONS UNDER PART 500 § 501.3 Replacement bags for vacuum cleaners. Replacement bags for vacuum cleaners, packaged and labeled for retail sale are exempt from the requirements of § 500.15a...

  8. 16 CFR 501.3 - Replacement bags for vacuum cleaners.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Replacement bags for vacuum cleaners. 501.3... REQUIREMENTS AND PROHIBITIONS UNDER PART 500 § 501.3 Replacement bags for vacuum cleaners. Replacement bags for vacuum cleaners, packaged and labeled for retail sale are exempt from the requirements of § 500.15a...

  9. 16 CFR 501.3 - Replacement bags for vacuum cleaners.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Replacement bags for vacuum cleaners. 501.3... REQUIREMENTS AND PROHIBITIONS UNDER PART 500 § 501.3 Replacement bags for vacuum cleaners. Replacement bags for vacuum cleaners, packaged and labeled for retail sale are exempt from the requirements of § 500.15a...

  10. 16 CFR 501.3 - Replacement bags for vacuum cleaners.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Replacement bags for vacuum cleaners. 501.3... REQUIREMENTS AND PROHIBITIONS UNDER PART 500 § 501.3 Replacement bags for vacuum cleaners. Replacement bags for vacuum cleaners, packaged and labeled for retail sale are exempt from the requirements of § 500.15a...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 30 CFR 57.19028 - End attachment replacement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false End attachment replacement. 57.19028 Section 57.19028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL... Hoisting Wire Ropes § 57.19028 End attachment replacement. Wire rope attachments shall be replaced...

  18. 30 CFR 56.19028 - End attachment replacement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false End attachment replacement. 56.19028 Section 56.19028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL... Wire Ropes § 56.19028 End attachment replacement. Wire rope attachments shall be replaced when...

  19. 30 CFR 75.1438 - End attachment replacement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false End attachment replacement. 75.1438 Section 75.1438 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND... attachment replacement. Wire rope attachments shall be replaced when cracked, deformed, or excessively worn....

  20. 25 CFR 700.95 - Replacement housing funds.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Replacement housing funds. 700.95 Section 700.95 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.95 Replacement housing funds. Replacement...