Renal homotransplantation in pediatric patients.

Fifty-seven patients were treated with renal homotransplantation from 1½ to 7⅔ years ago; 23 patients were 12 years or younger and the other 34 patients were 13 to 18. Family members (usually parents) were the primary donors in 45 cases. Unrelated volunteers or cadavers donated the other 12 homografts. Immunosuppression was with azathioprine and prednisone, and in some cases also with ALG. Forty-two of the 57 recipients survived for at least 1 year. Additional deaths occurred at 17½ and 19 months leaving 40 recipients (70.2%) alive. Six survivors had successful retransplantation following late failure of their original homografts. Control of rejection was not particularly different than in adult cases. “Homograft glomerulonephritis” was found in chronically tolerated transplants, but no more frequently than in older patients. Many postoperative problems in the pediatric age group were the consequence of retardation of growth caused either by pre-existing uremia or by the need for high dose postoperative steroid therapy, orthopedic accidents such as femoral and vertebral fractures, and psychiatric complications which led to two suicides. In spite of these difficulties, the meaningful rehabilitation that was obtained in the chronic survivors makes us regard pediatric patients as favorable candidates for therapy with renal transplantation

Assessment of the Introductory Transportation Engineering Course and the General Transportation Engineering Curriculum

Transportation engineering is a critical subdiscipline of the civil engineering profession as indicated by its inclusion on the Fundamentals of Engineering Examination, its overlap with other specialty areas of civil engineering, and as recognized by the Transportation Research Board, Institute of Transportation Engineers, and the American Society of Civil Engineers. With increasing transportation workforce needs, low numbers of students entering the ‘pipeline’, and limited hours within undergraduate civil engineering programs, it is important to ensure civil engineering students receive adequate preparation and exposure to career opportunities in the transportation engineering field. As such, investigations into the status of transportation engineering within civil engineering programs and specifically the introductory transportation engineering course are essential for understanding the implications to the profession. This paper presents a review of relevant literature and findings from a new survey of ABET-accredited civil engineering programs that yielded 84 responses. The survey indicates that 88 percent of responding programs teach an introductory course in transportation engineering, and 79 percent require it in their undergraduate programs. There is significant variation in the structure of the introductory course (number of credit hours, lab requirements, etc.), and common responses regarding improvements that could be made include adding labs, requiring a second course, and broadening course content. In addition, nearly 15 percent of instructors teaching the introductory course did not have a primary focus in transportation engineering. This finding should be investigated further, given that this course may be an undergraduate civil engineering student’s only exposure to the profession.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the Transportation Research Board of the National Academies and can be found at: https://doi.org/10.3141/2328-0

A series of algebras generalizing the octonions and Hurwitz-Radon identity

International audienceWe study non-associative twisted group algebras over (ℤ2)n with cubic twisting functions. We construct a series of algebras that extend the classical algebra of octonions in the same way as the Clifford algebras extend the algebra of quaternions. We study their properties, give several equivalent definitions and prove their uniqueness within some natural assumptions. We then prove a simplicity criterion. We present two applications of the constructed algebras and the developed technique. The first application is a simple explicit formula for the following famous square identity: (a21+⋯+a2N)(b21+⋯+b2ρ(N))=c21+⋯+c2N , where c k are bilinear functions of the a i and b j and where ρ(N) is the Hurwitz-Radon function. The second application is the relation to Moufang loops and, in particular, to the code loops. To illustrate this relation, we provide an explicit coordinate formula for the factor set of the Parker loop

Mechanisms of adverse effects of anti-VEGF therapy for cancer

Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways important in the regulation and maintenance of the microvasculature. Downregulation of these pathways in normal organs can lead to vascular disturbances and even regression of blood vessels, which could be intensified by concurrent pathological conditions. These changes are generally manageable and pose less risk than the tumours being treated, but they highlight the properties shared by tumour vessels and the vasculature of normal organs

Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies

<p>Abstract</p> <p>Background</p> <p>YN968D1 (Apatinib) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies.</p> <p>Methods</p> <p>This dose-escalation study was conducted according to the Chinese State Food and Drug Administration (SFDA) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death.</p> <p>Results</p> <p>Forty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension (69.5%, 29 grade 1-2 and 3 grade 3-4), proteinuria (47.8%, 16 grade 1-2 and 6 grade 3-4), and hand-foot syndrome (45.6%, 15 grade 1-2 and 6 grade 3-4). Among the thirty-seven evaluable patients, PR was noted in seven patients (18.9%), SD 24 (64.9%), with a disease control rate of 83.8% at 8 weeks.</p> <p>Conclusions</p> <p>The recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations.</p> <p>Trial registration</p> <p>ClinicalTrials.gov unique identifier: NCT00633490</p

A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain

<p>Abstract</p> <p>Background</p> <p>Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.</p> <p>Methods</p> <p>Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.</p> <p>Results</p> <p>Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.</p> <p>Conclusions</p> <p>This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00566930">NCT00566930</a></p

Efficacy of manipulation for non-specific neck pain of recent onset: design of a randomised controlled trial

BACKGROUND: Manipulation is a common treatment for non-specific neck pain. Neck manipulation, unlike gentler forms of manual therapy such as mobilisation, is associated with a small risk of serious neurovascular injury and can result in stroke or death. It is thought however, that neck manipulation provides better results than mobilisation where clinically indicated. There is long standing and vigorous debate both within and between the professions that use neck manipulation as well as the wider scientific community as to whether neck manipulation potentially does more harm than good. The primary aim of this study is to determine whether neck manipulation provides more rapid resolution of an episode of neck pain than mobilisation. METHODS/DESIGN: 182 participants with acute and sub-acute neck pain will be recruited from physiotherapy, chiropractic and osteopathy practices in Sydney, Australia. Participants will be randomly allocated to treatment with either manipulation or mobilisation. Randomisation will occur after the treating practitioner decides that manipulation is an appropriate treatment for the individual participant. Both groups will receive at least 4 treatments over 2 weeks. The primary outcome is number of days taken to recover from the episode of neck pain. Cox regression will be used to compare survival curves for time to recovery for the manipulation and mobilisation treatment groups. DISCUSSION: This paper presents the rationale and design of a randomised controlled trial to compare the effectiveness of neck manipulation and neck mobilisation for acute and subacute neck pain

The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer continues to have a 5-year survival of less than 5%. Therefore, more effective therapies are necessary to improve prognosis in this disease. Angiogenesis is required for tumor growth, and subsequently, mediators of angiogenesis are attractive targets for therapy. Vascular endothelial growth factor (VEGF) is a well-characterized mediator of tumor angiogenesis that functions primarily by binding and activating VEGF receptor 2 (VEGFR2). In this study, we evaluate the use of CT-322, a novel biologic (Adnectin). This small protein is based on a human fibronectin domain and has beneficial properties in that it is fully human, stable, and is produced in bacteria. CT-322 binds to and inhibits activation of VEGFR2.</p> <p>Methods</p> <p>The efficacy of CT-322 was evaluated <it>in vivo </it>using two orthotopic pancreatic tumor models. The first model was a human tumor xenograft where MiaPaCa-2 cells were injected into the tail of the pancreas of nude mice. The second model was a syngeneic tumor using Pan02 cells injected into pancreas of C57BL/6J mice. In both models, therapy was initiated once primary tumors were established. Mice bearing MiaPaCa-2 tumors were treated with vehicle or CT-322 alone. Gemcitabine alone or in combination with CT-322 was added to the treatment regimen of mice bearing Pan02 tumors. Therapy was given twice a week for six weeks, after which the animals were sacrificed and evaluated (grossly and histologically) for primary and metastatic tumor burden. Primary tumors were also evaluated by immunohistochemistry for the level of apoptosis (TUNEL), microvessel density (MECA-32), and VEGF-activated blood vessels (Gv39M).</p> <p>Results</p> <p>Treatment with CT-322 was effective at preventing pancreatic tumor growth and metastasis in orthotopic xenograft and syngeneic models of pancreatic cancer. Additionally, CT-322 treatment increased apoptosis, reduced microvessel density and reduced the number of VEGF-activated blood vessels in tumors. Finally, CT-322, in combination with gemcitabine was safe and effective at controlling the growth of syngeneic pancreatic tumors in immunocompetent mice.</p> <p>Conclusion</p> <p>We conclude that CT-322 is an effective anti-VEGFR2 agent and that further investigation of CT-322 for the treatment of pancreatic cancer is warranted.</p

Prospective randomized trial evaluating mandatory second look surgery with HIPEC and CRS vs. standard of care in patients at high risk of developing colorectal peritoneal metastases

<p>Abstract</p> <p>Background</p> <p>The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.</p> <p>Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance.</p> <p>Methods/Design</p> <p>This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: NCT01095523</p