Successful Treatment of Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial.

PubMed

Sahebnasagh, Adeleh; Ghasemi, Arash; Akbari, Jafar; Alipour, Abbas; Lashkardoost, Hossein; Ala, Shahram; Salehifar, Ebrahim

2017-11-01

Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area. In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46-72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0-4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home). There was a significant (p < 0.05) improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for "clinical presentation total" and "RTOG total" were 3.97 (1.3-11.9) and 5.9 (1.6-21.6), respectively. A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.

Flagellin preconditioning enhances the efficacy of mesenchymal stem cells in an irradiation-induced proctitis model.

PubMed

Linard, Christine; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Benderitter, Marc

2016-09-01

The success of mesenchymal stem cell transplantation for proctitis depends not only on cell donors but also on host microenvironmental factors, which play a major role in conditioning mesenchymal stem cell immunosuppressive action and repair. This study sought to determine if flagellin, a TLR5 ligand, can enhance the mesenchymal stem cell treatment efficacy in radiation-induced proctitis. With the use of a colorectal model of 27 Gy irradiation in rats, we investigated and compared the effects on immune capacity and remodeling at 28 d after irradiation of the following: 1) systemic mesenchymal stem cell (5 × 10(6)) administration at d 7 after irradiation, 2) administration of flagellin at d 3 and systemic mesenchymal stem cell administration at d 7, and 3) in vitro preconditioning of mesenchymal stem cells with flagellin, 24 h before their administration on d 7. The mucosal CD8(+) T cell population was normalized after treatment with flagellin-preconditioned mesenchymal stem cells or flagellin plus mesenchymal stem cells, whereas mesenchymal stem cells alone did not alter the radiation-induced elevation of CD8(+) T cell frequency. Mesenchymal stem cell treatment returned the irradiation-elevated frequency of CD25(+) cells in the mucosa-to-control levels, whereas both flagellin-preconditioned mesenchymal stem cell and flagellin-plus-mesenchymal stem cell treatment each significantly increased not only CD25(+) cell frequency but also forkhead box p3 and IL-2Rα expression. Specifically, IL-10 was overexpressed after flagellin-preconditioned mesenchymal stem cell treatment. Analysis of collagen expression showed that the collagen type 1/collagen type 3 ratio, an indicator of wound-healing maturation, was low in the irradiated and mesenchymal stem cell-treated groups and returned to the normal level only after the flagellin-preconditioned mesenchymal stem cell treatment. This was associated with a reduction in myofibroblast accumulation. In a proctitis model, flagellin-preconditioned mesenchymal stem cells improved colonic immune capacity and enhanced tissue remodeling. © Society for Leukocyte Biology.

Reducing Toxicity of Radiation Treatment of Advanced Prostate Cancer

DTIC Science & Technology

2014-10-01

Figure 1: Radioprotective effects of RTA 408 and DMAPT. (A) C57Bl/6 mice ( n =5 per cohort) were administered RTA 408 (17.5 mg/kg i.p.) or DMAPT...INVENTIONS, PATENTS AND LICENSES: N /A 8. REPORTABLE OUTCOMES: This award has led to unique insights into the mechanism of action by which certain...Radiation Oncology, Biology, Physics 70:90-95. 2. Hovdenak, N ., Sorbye, H., and Dahl, O. 2005. Sucralfate does not ameliorate acute radiation proctitis

Sexually Transmitted Diseases

DTIC Science & Technology

1989-12-01

fever , abdominal pain, tenderness on pelvic examination e. pharyngitis, proctitis--same as males--may lead to dissemination (11-15) Diagnosis (16) 1...weeks after chancre b. may show fever , malaise, headache, sore throat c. generalized lymphadenopathy, patchy hair loss d. rash--reddish,pink or coppery...nodes lead to sinus tract formation d. fever , chills, generalized rash--erythema nodosum or multiforme e. late complications include strictures or

Proctitis

MedlinePlus

... This can occur in infants who drink either cow's milk- or soy-based formula, and in those who are breastfed by mothers who eat dairy products. Eosinophilic proctitis. A form of proctitis caused ...

Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

PubMed

Li, Guang-hui; Wang, Dong-lin; Hu, Yi-de; Pu, Ping; Li, De-zhi; Wang, Wei-dong; Zhu, Bo; Hao, Ping; Wang, Jun; Xu, Xian-qiong; Wan, Jiu-qing; Zhou, Yi-bing; Chen, Zheng-tang

2010-09-01

Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant complication of abdominal or pelvic radiation. Considering the negative impact of RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS in patients were investigated. Thirty-six patients with seminoma or lymphomas were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two patients with cervical cancer were randomized to a trial group (n = 21) and control group (n = 21). Radiotherapy used a parallel opposed anterior and posterior. 300-mg berberine was administered orally three times daily in trial groups. Eight patients with RIAIS were treated with 300-mg berberine three times daily from the third to the fifth week. Toxicities, such as fatigue, anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients with abdominal/pelvic radiation in the control group showed grade 1 fatigue, anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2 anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue, colitis, anorexia/nausea, and proctitis occurred in patients of pelvic radiotherapy treated with berberine. Pretreatment with berberine significantly decreased the incidence and severity of RIAIS in patients with abdominal/pelvic radiotherapy when compared with the patients of the control group (P < 0.05). RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after receiving berberine treatment. Berberine significantly reduced the incidence and severity of RIAIS and postponed the occurrence of RIAIS in patients with abdominal or whole pelvic radiation.

Analysis and Management of Rectal Gas with Kampo Formulas During Intensity-Modulated Radiotherapy of Prostate Cancer: A Case Series Study.

PubMed

Nagai, Aiko; Shibamoto, Yuta; Ogawa, Keiko; Inoda, Koji; Yoshida, Masanori; Kikuchi, Yuzo

2016-06-01

During intensity-modulated radiation therapy (IMRT) for prostate cancer, the target, bladder, and rectum positions should be kept constant to reduce adverse events, such as radiation proctitis, and to increase local tumor control. For this purpose, decreasing the rectal contents as much as possible is important. Daisaikoto (DST) and bukuryoingohangekobokuto (BIHKT) are traditional Japanese herbal (Kampo) formulas that have been used to treat patients with abdominal bloating or constipation. This study investigated the effect of DST and BIHKT on the rectal gas volume during prostate IMRT according to Kampo diagnosis. Five patients were treated with DST or BIHKT at a dose of 5.0 or 7.5 g/d. The volume of rectal gas in 189 megavoltage computed tomographic images taken before each treatment session and the frequency of rectal gas drainage were evaluated before and after DST or BIHKT administration. After DST or BIHKT treatment, the mean volume of rectal gas was reduced from 6.4 to 2.1 mL, and the mean frequency of gas drainage decreased from 43% to 9%. DST and BIHKT appear to be useful in reducing rectal gas, which would help prevent radiation proctitis and improve the local control of prostate cancer with IMRT.

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

Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it; Cilla, Savino; Deodato, Francesco

Purpose: A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes. Methods and Materials: Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort receivedmore » higher doses (60 Gy in 2.4-Gy fractions). Results: Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age-Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose (P=.001); not so enterocolitis. Grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade ≥3 GI or grade ≥2 GU toxicity. The 3-year late grade ≥2 GI and GU toxicity–free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0). Conclusions: This clinical study showed the feasibility of this technique and its good profile in terms of acute and late toxicity at the recommended doses even in aged and frail patients.« less

Endoscopic diode laser therapy for chronic radiation proctitis.

PubMed

Polese, Lino; Marini, Lucia; Rizzato, Roberto; Picardi, Edgardo; Merigliano, Stefano

2018-01-01

The purpose of this study is to determine the effectiveness of endoscopic diode laser therapy in patients presenting rectal bleeding due to chronic radiation proctitis (CRP). A retrospective analysis of CRP patients who underwent diode laser therapy in a single institution between 2010 and 2016 was carried out. The patients were treated by non-contact fibers without sedation in an outpatient setting. Fourteen patients (median age 77, range 73-87 years) diagnosed with CRP who had undergone high-dose radiotherapy for prostatic cancer and who presented with rectal bleeding were included. Six required blood transfusions. Antiplatelet (three patients) and anticoagulant (two patients) therapy was not suspended during the treatments. The patients underwent a median of two sessions; overall, a mean of 1684 J of laser energy per session was used. Bleeding was resolved in 10/14 (71%) patients, and other two patients showed improvement (93%). Only one patient, who did not complete the treatment, required blood transfusions after laser therapy; no complications were noted during or after the procedures. Study findings demonstrated that endoscopic non-contact diode laser treatment is safe and effective in CRP patients, even in those receiving antiplatelet and/or anticoagulant therapy.

Herpes simplex virus proctitis in homosexual men. Clinical, sigmoidoscopic, and histopathological features.

PubMed

Goodell, S E; Quinn, T C; Mkrtichian, E; Schuffler, M D; Holmes, K K; Corey, L

1983-04-14

Acute herpes simplex virus (HSV) infection was detected in 23 of 102 consecutively examined, sexually active male homosexuals who presented with anorectal pain, discharge, tenesmus, or hematochezia, as compared with 3 of 75 homosexual men without gastrointestinal symptoms (P less than 0.01). Findings that were significantly more frequent in men with HSV proctitis than in men with proctitis due to other infectious causes included fever (48 per cent), difficulty in urinating (48 per cent), sacral paresthesias (26 per cent), inguinal lymphadenopathy (57 per cent), severe anorectal pain (100 per cent), tenesmus (100 per cent), constipation (78 per cent), perianal ulcerations (70 per cent), and the presence of diffuse ulcerative or discrete vesicular or pustular lesions in the distal 5 cm of the rectum (50 per cent). Serologic evidence indicated that 85 per cent of the men with symptomatic HSV proctitis were having their first episode of HSV-2 infection. The diagnosis of HSV proctitis is suggested by the presence of severe anorectal pain, difficulty in urinating, sacral paresthesias or pain, and diffuse ulceration of the distal rectal mucosa.

Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding

PubMed Central

Weiner, Joseph Paul; Wong, Andrew Thomas; Schwartz, David; Martinez, Manuel; Aytaman, Ayse; Schreiber, David

2016-01-01

Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient’s symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases. PMID:27610010

Proctitis

MedlinePlus

... of proctitis. They can be grouped as follows: Inflammatory bowel disease Autoimmune disease Harmful substances Non-sexually transmitted infection ... the rectum. Risk factors include: Autoimmune disorders , including inflammatory bowel disease High-risk sexual practices, such as anal sex ...

Evaluation of prophylactic and therapeutic effects of ruscogenin on acute radiation proctitis: an experimental rat model.

PubMed

Yavuz, Erkan; Karagulle, Onur Olgac; Ercan, Gulcin; Celik, Atilla; Yigitbas, Hakan; Bayrak, Busra Yaprak; Tartar, Rumeysa; Kusaslan, Ramazan; Altinel, Yuksel; Gulcicek, Osman Bilgin

2018-04-01

Radiation proctitis (RP) is inflammation and damage to the rectum, manifested secondary to ionizing radiation utilized for treatment. In this study, we evaluated the anti-inflammatory therapeutical and protective effects of ruscogenin in a model of acute RP. Thirty-two Sprague-Dawley rats were divided into 4 groups (n = 8) as sham, control, treatment, and prophylaxis groups. Prophylaxis group and treatment group were dosed ruscogenin by oral gavage for 14 days pre- and postradiation. At the end of the 28th day, all subjects were sacrificed. Histopathological analysis showed a significant increase in cryptitis abscess, cryptitis and reactive atypia, and depth of lymphocytic infiltration of the control group, compared to the other groups (P < 0.05), while treatment and prophylaxis groups showed significant decreases (P < 0.05). Immunohistochemical analysis indicated that immunoreactivity were significantly higher in control group (P < 0.05, P < 0.001, and P < 0.01, respectively), but vice versa for treatment and prophylaxis groups. There was not any significant difference for fibroblast growth factor 2 immunoreactivity. The epithelium of control rectums indicated an increase in TNF-α immunoreactivity while other groups had significant decrease (P < 0.01). Electron microscopical findings were parallel to light microscopy. In this study, ruscogenin was observed to be effective on prophylaxis or treatment of acute RP. Although there are various reports on the treatment of the rectum damaged by acute RP in the literature, this could be the first study since there is no research indicating the ultrastructural effect of ruscogenin.

Chlamydia trachomatis proctitis masquerading as carcinoma rectum: First case report from India.

PubMed

Dhawan, Benu; Makharia, Govind Kumar; Juyal, Deepak; Sebastian, Sujeesh; Bhatia, Riti; Khanna, Neena

2017-01-01

While proctitis is caused both by infectious and noninfectious causes, infectious causes are acquired typically sexually. Chlamydia trachomatis, which is the most frequent bacterial pathogen causing sexually transmitted infections worldwide, is one of the causative agents of proctitis. We report a case history of a bisexual male who presented to us with rectal bleeding. The colonoscopy showed a nodular ulcerated lesion in the rectum suggestive of rectal malignancy, but biopsies from rectal mass did not reveal malignancy. A rectal biopsy was positive for C. trachomatis by polymerase chain reaction assay, and a diagnosis of C. trachomatis proctitis was made. Considering the invasive anorectal disease and patient's sexual history, he was treated with prolonged doxycycline therapy as per Centres for Disease Control and Prevention's treatment recommendation for lymphogranuloma venereum. A high index of clinical suspicion along with appropriate microbiological testing can clinch the diagnosis of C. trachomatis infection.

Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

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

Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R., E-mail: ms@ctu.mrc.ac.u

2010-07-01

Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Managementmore » (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.« less

Up-Regulation of Endothelin Type A Receptor in Human and Rat Radiation Proctitis: Preclinical Therapeutic Approach With Endothelin Receptor Blockade

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

Jullien, Nicolash; Blirando, Karl; Milliat, Fabien

2009-06-01

Purpose: Rectum radiation damage and fibrosis are often associated with radiation therapy of pelvic tumors. The endothelin (ET) system has been implicated in several fibrotic diseases but never studied in the context of gastrointestinal radiation damage. This study assessed modifications in ET type 1 (ET-1), ET type A receptor (ET{sub A}), and ET type B receptor (ET{sub B}) localization and/or expression in irradiated human rectal tissue and in a rat model of delayed colorectal injury. We also evaluated the therapeutic potential of long-term ET receptor blockade. Methods and Materials: Routine histological studies of sections of healthy and radiation-injured human rectummore » tissue were done; the sections were also immunostained for ET{sub A} and ET{sub B} receptors. The rat model involved the delivery of 27 Gy in a single dose to the colons and rectums of the animals. The ET-1/ET{sub A}/ET{sub B} expression and ET{sub A}/ET{sub B} localization were studied at 10 weeks postexposure. The abilities of bosentan and atrasentan to protect against delayed rectal injury were also investigated. Results: The immunolocalization of ET{sub A} and ET{sub B} in healthy human rectums was similar to that in rat rectums. However, strong ET{sub A} immunostaining was seen in the presence of human radiation proctitis, and increased ET{sub A} mRNA levels were seen in the rat following colorectal irradiation. Immunostaining for ET{sub A} was also strongly positive in rats in areas of radiation-induced mucosal ulceration, atypia, and fibroproliferation. However, neither bosentan nor atrasentan prevented radiation damage to the rectum when given long term. The only effect seen for atrasentan was an increased number of sclerotic vessel sections in injured tissues. Conclusions: As the result of the overexpression of ET{sub A}, radiation exposure deregulates the endothelin system through an 'ET{sub A} profile' in the human and rodent rectum. However, therapeutic interventions involving mixed or specific ET{sub A} receptor blockade do not prevent radiation damage. Further studies are necessary to identify the precise roles of ET in the gastrointestinal response to radiation exposure.« less

Phase II Study of Long-Term Androgen Suppression With Bevacizumab and Intensity-Modulated Radiation Therapy (IMRT) in High-Risk Prostate Cancer

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

Vuky, Jacqueline, E-mail: vukyja@ohsu.edu; Pham, Huong T.; Warren, Sarah

Purpose: We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer. Methods and Materials: We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes.more » Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities. Results: The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28-40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%). Conclusions: Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be performed cautiously.« less

Lymphogranuloma venereum proctitis

PubMed Central

Harrison, Tucker; Stroup, Jeff

2016-01-01

We describe a 60-year-old man who presented with rectal pain and bleeding of a month's duration. His presentation was highly suggestive of lymphogranuloma venereum (LGV) proctitis. Nucleic acid amplification for chlamydia and gonorrhea via rectal swab revealed evidence supportive of anorectal chlamydia. Treatment with doxycycline resulted in complete resolution of his symptoms. PMID:27695183

Pathophysiology and Natural History of Anorectal Sequelae Following Radiation Therapy for Carcinoma of the Prostate

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

Yeoh, Eric K., E-mail: eric.yeoh@health.sa.gov.au; Discipline of Medicine, University of Adelaide, Adelaide; Holloway, Richard H.

2012-12-01

Purpose: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. Methods and Materials: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activitiesmore » of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. Results: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. Conclusions: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.« less

A Prospective Cohort Study to Compare Treatment Results Between 2 Fractionation Schedules of High-Dose-Rate Intracavitary Brachytherapy (HDR-ICBT) in Patients With Cervical Cancer

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

Huang, Eng-Yen; School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Taiwan; Sun, Li-Min

Purpose: To compare the treatment results of 2 fractionation schedules for high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. Methods and Materials: From June 2001 through January 2008, 267 patients with stage IB-IVA cervical cancer were enrolled in the study. All patients underwent 4-field pelvic irradiation and HDR-ICBT. The median central and parametrial doses were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy Multiplication-Sign 4 (HDR-4) (n=144) or 4.5 Gy Multiplication-Sign 6 (HDR-6) (n=123) to point A of ICBT using {sup 192}Ir isotope twice weekly. The rates of overall survival, locoregional failure, distant metastasis, proctitis, cystitis,more » and enterocolitis were compared between HDR-4 and HDR-6. Results: There were no significant differences in the demographic data between HDR-4 and HDR-6 except for total treatment time. The 5-year proctitis rates were 23.0% and 21.5% in HDR-4 and HDR-6 (P=.399), respectively. The corresponding rates of grade 2-4 proctitis were 18.7% and 9.6% (P=.060). The corresponding rates of grades 3-4 proctitis were 5.2% and 1.3% (P=.231). Subgroup analysis revealed that HDR-4 significantly increased grade 2-4 proctitis in patients aged {>=}62 years old (P=.012) but not in patients aged <62 years (P=.976). The rates of overall survival, locoregional failure, distant metastasis, cystitis, and enterocolitis were not significantly different between HDR-4 and HDR-6 schedules. Conclusion: The small fraction size of HDR-ICBT is associated with grade 2 proctitis without compromise of prognosis in elderly patients. This schedule is suggested for patients who tolerate an additional 2 applications of HDR-ICBT.« less

[Gonorrheal proctitis imitating proctalgia fugax].

PubMed

Nechvátal, A; Masek, T; Hoch, J; Hercogová, J

2004-01-01

Proctalgia fugax is usually a source of many diagnostic and therapeutic problems. It is often very difficult to find the cause of the pain. Case-report of a 27-year-old patient who was examined by surgeons on cramp-like pain localized to the rectum. The careful history and laboratory examination confirmed gonorrheal proctitis. She was then successfully treated with ceftriaxon.

Efficacy and Safety of Mesalamine Suppositories for Treatment of Ulcerative Proctitis in Children and Adolescents

PubMed Central

Heyman, Melvin B.; Kierkus, Jaroslaw; Spénard, Jean; Shbaklo, Hadia; Giguere, Monique

2011-01-01

Background Treatment of ulcerative proctitis has not been well studied in pediatric populations. We conducted an open-label trial to evaluate the clinical efficacy of a mesalamine suppository (500 mg) to treat pediatric patients with mild to moderate ulcerative proctitis. Methods Pediatric patients (5–17 years of age) with ulcerative proctitis were enrolled for baseline evaluations, including a flexible sigmoidoscopic (or colonoscopic) assessment with biopsies performed at study entry. Eligible patients were started on mesalamine suppositories (500 mg) at bedtime. Two follow-up visits were scheduled after 3 and 6 weeks of treatment. The dose could be increased to 500 mg twice daily at the week 3 follow-up visit if deemed appropriate by the investigator based on the Disease Activity Index (DAI) assessment. The primary outcome measure was a DAI derived from a composite score of stool frequency, urgency of defecation, rectal bleeding, and general well-being. Results Forty-nine patients were included in the intent-to-treat analysis. The mean DAI value decreased from 5.5 at baseline to 1.6 and 1.5 at weeks 3 and 6, respectively (P < 0.0001). Only 4 patients had their dose increased to 500 mg twice daily at week 3. Forty-one patients experienced at least one adverse event, most of which were deemed mild and unrelated to study therapy. The most common treatment-emergent adverse events were gastrointestinal (n = 30, 61.2%). Conclusions This study showed that a daily bedtime dose of a 500 mg mesalamine suppository is safe and efficacious in children with ulcerative proctitis. PMID:20848454

Ulcerative proctitis: an update on the pharmacotherapy and management.

PubMed

Gecse, Krisztina B; Lakatos, Peter L

2014-08-01

Ulcerative colitis (UC) presents as proctitis in approximately a quarter of the patients. It may progress into left-sided or extensive colitis in up to 50% of cases upon long-term follow-up. Currently available data on ulcerative proctitis are summarized and critically reviewed. Extensive literature search (MEDLINE) was performed to identify relevant articles up to March 2014. The short-term goal of the treatment in UC is to induce remission, whereas long-term goals are to maintain remission and prevent disease progression. Topically administered 5-aminosalicylates (5-ASA) and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice. Locally administered 5-ASA preparations are more effective than oral compounds. The combination of topical and oral 5-ASA and steroids should be considered for escalation of treatment. Refractory patients should be re-evaluated to exclude for compliance failures, infections or proximal disease extent. True refractory or steroid-dependent patients may require immunomodulators or biological therapy. Alternative medicine can be used complementarily, while experimental approaches are reserved for patients failing conventional medication. Proctocolectomy may be the last resort of treatment. Upon long-term, 5-ASA maintenance treatment is indicated in all UC cases to prevent relapse and disease progression.

Clinical comparison of two linear-quadratic model-based isoeffect fractionation schemes of high-dose-rate intracavitary brachytherapy for cervical cancer.

PubMed

Wang, Chong-Jong; Huang, Eng-Yen; Sun, Li-Min; Chen, Hui-Chun; Fang, Fu-Min; Hsu, Hsuan-Chih; Changchien, Chan-Chao; Leung, Stephen Wan

2004-05-01

Two linear-quadratic model-based isoeffect fractionation schemes of high-dose-rate intracavitary brachytherapy (HDR-IC) were used to treat cervical cancer in two consecutive periods. Patient outcomes and complications were analyzed and compared. Between November 1987 and December 1996, a total of 541 women diagnosed with cervical cancer were treated with curative-intent radiotherapy. Patients were categorized into two groups according to the two isoeffect schemes used. Group 1 consisted of 254 patients treated with external beam radiotherapy (EBRT) plus 7.2 Gy HDR-IC to Point A for three fractions in the first period. Group 2 consisted of 284 patients treated with EBRT plus 4.8 Gy HDR-IC for five fractions in the second period. The goal of the new scheme for the latter group was to deliver an isoeffect dose that maintained similar tumor control but reduced normal tissue complications. The calculated biologically effective dose (BED(10), assuming an alpha/beta ratio = 10) of EBRT plus HDR-IC for tumor and acute responding tissue in Groups 1 and 2 was 90 Gy(10) (52.8 + 37.2 Gy) and 88.6 Gy(10) (53.1 + 35.5 Gy), respectively. The corresponding BED(3) for late responding tissue (assuming an alpha/beta ratio = 3) in Groups 1 and 2 was 146.7 Gy(3) (73.3 + 73.4 Gy) and 134.4 Gy(3) (72 + 62.4 Gy), respectively. Patients were followed for 6.1-15.2 years (median, 9.8 years). Overall, 66 patients (12.2%) developed pelvic recurrence. Of these, 53 patients had central recurrence. Of the 53 patients with central recurrence, 24 (9.4%) were in Group 1 and 29 (10.1%) in Group 2 (p = 0.722). The actuarial pelvic control rate for Groups 1 and 2 was 88.2% and 86.3% at 5 years and 87.3% and 85.5% at 10 years, respectively (p = 0.504). The actuarial overall survival rate for Groups 1 and 2 was 63.5% and 56.1% at 5 years and 47.8% and 49.3% at 10 years, respectively (p = 0.734). The actuarial proctitis rate for Groups 1 and 2 was 49.7% and 32.7% at 5 years and 50.5% and 32.7% at 10 years, respectively (p <0.001). Most of the decrease in the rate of proctitis was a result of a decrease in the incidence of low-grade proctitis (38% vs. 22%). The incidence of high-grade complications remained unchanged, 8% vs. 7%. The actuarial cystitis rate for Groups 1 and 2 was 14.3% vs. 11.4% at 5 years and 24.1% vs. 15% at 10 years, respectively (p = 0.134). Multivariate analysis revealed that the fractionation scheme (three fractions vs. five fractions) was a significant factor influencing the proctitis rate (p = 0.004, hazard ratio = 0.807; 95% confidence interval, 0.697-0.934), but not the local pelvic control rate, overall survival rate, or cystitis rate. The treatment results of the two groups maintained similar outcomes, while the complications decreased. The linear-quadratic model correctly predicted this outcome. Biologically, the manipulation of the fraction size in our study suggested that the sensitivity of the late responding tissue to the fractional change from 7.2 Gy to 4.8 Gy in HDR-IC is high and detectable clinically. The success, however, had its limitations, and the improvement was confined to low-grade complications.

The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

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

Vuong, Te, E-mail: tvuong@jgh.mcgill.ca; Waschke, Kevin; Niazi, Tamim

Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receivemore » the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.« less

Chlamydial Proctitis in a Young Man Who Has Sex with Men: Misdiagnosed as Inflammatory Bowel Disease.

PubMed

Lee, Kyung Jin; Kim, Jaeyeon; Shin, Dong Hwan; Jung, Jun Oh; Koh, Seokyoung; Kim, Ka Young; Lee, Jae Min

2015-12-01

We report the case of a 20-year-old man with a 2-month history of anal pain and bloody rectal discharge. He was referred to our clinic of gastroenterology for suspected inflammatory bowel disease (IBD). The colonoscopy showed mucosal nodularities on the rectum and an anal tag. Because the colonoscopic findings were not consistent with the typical manifestations of IBD, we took an additional sexual history and performed studies for infectious proctitis, including serologic tests for Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum. He had homosexual experience, and the serologic tests and PCR of a rectal swab were positive for C. trachomatis infection. Finally he was diagnosed as having chlamydial proctitis and was treated with intramuscular ceftriaxone 250 mg in a single dose and doxycycline 100 mg orally twice daily for 7 days. After 2 months, he had no lower abdominal symptoms and his endoscopic findings were improved.

A feasibility study of [sup 252]Cf neutron brachytherapy, cisplatin + 5-FU chemo-adjuvant and accelerated hyperfractionated radiotherapy for advanced cervical cancer

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

Murayama, Y.; Wierzbicki, J.; Bowen, M.G.

The purpose was to evaluate the feasibility and toxicity of [sup 252]Cf neutron brachytherapy combined with hyperaccelerated chemoradiotherapy for Stage III and IV cervical cancers. Eleven patients with advanced Stage IIIB-IVA cervical cancers were treated with [sup 252]Cf neutron brachytherapy in an up-front schedule followed by cisplatin (CDDP; 50 mg/m[sup 2]) chemotherapy and hyperfractionated accelerated (1.2 Gy bid) radiotherapy given concurrently with intravenous infusion of 5-Fluorouracil (5-FU) (1000 mg/m[sup 2]/day [times] 4 days) in weeks 1 and 4 with conventional radiation (weeks 2, 3, 5, and 6). Total dose at a paracervical point A isodose surface was 80-85 Gy-eq bymore » external and intracavitary therapy and 60 Gy at the pelvic sidewalls. Patients tolerated the protocol well. There was 91% compliance with the chemotherapy and full compliance with the [sup 252]Cf brachytherapy and the external beam radiotherapy. There were no problems with acute chemo or radiation toxicity. One patient developed a rectovaginal fistula (Grade 3-4 RTOG criteria) but no other patients developed significant late cystitis, proctitis or enteritis. There was complete response (CR) observed in all cases. With mean follow-up to 26 months, local control has been achieved with 90% actuarial 3-year survival with no evidence of disease (NED). [sup 252]Cf neutrons can be combined with cisplatin and 5-FU infusion chemotherapy plus hyperaccelerated chemoradiotherapy without unusual side effects or toxicity and with a high local response and tumor control rate. Further study of [sup 252]Cf neutron-chemoradiotherapy for advanced and bulky cervical cancer are indicated. The authors found chemotherapy was more effective with the improved local tumor control. 18 refs., 2 tabs.« less

Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

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

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; EMR3738, Université Lyon 1, Lyon; Decullier, Evelyne

Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Eventsmore » version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.« less

Case report: lymphogranuloma venereum proctitis-from rapid screening to molecular confirmation of a masked sexually transmitted disease.

PubMed

Markowicz, Mateusz; Grilnberger, Evelyn; Huber, Florian; Leibl, Gabriele; Abrahamian, Heidemarie; Gartner, Manfred; Huber, Monika; Chott, Andreas; Reiter, Michael; Stanek, Gerold

2013-08-01

Proctitis caused by Chlamydia trachomatis L2b can manifest with very mild, nonspecific symptoms, and appropriate diagnostic evaluation is crucial. The case report demonstrates that rapid screening test, detection of specific antibodies in serum, and direct pathogen identification by PCR performed on tissue sample or rectal swab allow successful diagnosis of the still emerging sexually transmitted disease among homosexual patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Gastrointestinal symptoms resembling ulcerative proctitis caused by larvae of the drone fly Eristalis tenax.

PubMed

Desoubeaux, Guillaume; Gaillard, Julien; Borée-Moreau, Diane; Bailly, Éric; Andres, Christian R; Chandenier, Jacques

2014-04-01

We report a case of facultative intestinal myiasis due to larvae of the drone fly Eristalis tenax, also named the rat-tailed maggots. The development of larvae in the lower bowel was responsible for non-specific gastrointestinal symptoms that resembled ulcerative proctitis. The diagnosis was established upon the observation of four spontaneously excreted mobile larvae. The definite identification of the E. tenax species was made possible by scanning electron microscopy. The clinical outcome was satisfactory.

Gastrointestinal symptoms resembling ulcerative proctitis caused by larvae of the drone fly Eristalis tenax

PubMed Central

Desoubeaux, Guillaume; Gaillard, Julien; Borée-Moreau, Diane; Bailly, Éric; Andres, Christian R; Chandenier, Jacques

2014-01-01

We report a case of facultative intestinal myiasis due to larvae of the drone fly Eristalis tenax, also named the rat-tailed maggots. The development of larvae in the lower bowel was responsible for non-specific gastrointestinal symptoms that resembled ulcerative proctitis. The diagnosis was established upon the observation of four spontaneously excreted mobile larvae. The definite identification of the E. tenax species was made possible by scanning electron microscopy. The clinical outcome was satisfactory. PMID:24766340

[Lymphogranuloma venereum: an emerging cause of proctitis in homosexual men in Barcelona].

PubMed

Vall-Mayans, M; Caballero, E

2009-02-01

Lymphogranuloma venereum (LGV) is a systemic sexually transmitted infection (STI) caused by Chlamydia trachomatis serovar L. Since 2003, outbreaks of LGV have been reported in homosexual men in Europe. The objective of this study is to describe an outbreak of LGV in Barcelona in 2007. Description of a clinical case series of confirmed LGV diagnosed in the STI clinic of Barcelona between September 2007 and January 2008. Seven cases have been confirmed up to January 31, 2008. All were homosexual men, with a mean age of 36, who were sexually promiscuous. Mean time of symptoms of proctitis was 28 days. All the patients were coinfected with human immunodeficiency virus (HIV) for an average period of 5 years. This outbreak is similar to other LGV outbreaks that are occurring in Europe. LGV should be considered in the differential diagnosis of proctitis in homosexual men and be treated with 100 mg of doxycycline/12 hours for three weeks. Preventive interventions directed at HIV infected persons are important.

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

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

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicitymore » questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.« less

Colostomy is a simple and effective procedure for severe chronic radiation proctitis.

PubMed

Yuan, Zi-Xu; Ma, Teng-Hui; Wang, Huai-Ming; Zhong, Qing-Hua; Yu, Xi-Hu; Qin, Qi-Yuan; Wang, Jian-Ping; Wang, Lei

2016-06-28

To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis (CRP). Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life before treatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during follow-up. Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission (94% vs 12%), especially in control of transfusion-dependent bleeding (100% vs 0%), and offered a better control of refractory perianal pain (100% vs 0%), and a lower score of bleeding (P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding (100% vs 21.5%, P = 0.002) and severe bleeding (100% vs 0%, P < 0.001), obtained a lower score of bleeding (0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels (P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammation cells, and massive fibrosis collagen depositions under the rectal wall, which revealed potential fibrosis formation. Diverting colostomy is a simple, effective and safe procedure for severe hemorrhagic CRP. Colostomy can improve quality of life and reduce serious complications secondary to radiotherapy.

Colostomy is a simple and effective procedure for severe chronic radiation proctitis

PubMed Central

Yuan, Zi-Xu; Ma, Teng-Hui; Wang, Huai-Ming; Zhong, Qing-Hua; Yu, Xi-Hu; Qin, Qi-Yuan; Wang, Jian-Ping; Wang, Lei

2016-01-01

AIM: To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis (CRP). METHODS: Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life before treatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during follow-up. RESULTS: Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission (94% vs 12%), especially in control of transfusion-dependent bleeding (100% vs 0%), and offered a better control of refractory perianal pain (100% vs 0%), and a lower score of bleeding (P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding (100% vs 21.5%, P = 0.002) and severe bleeding (100% vs 0%, P < 0.001), obtained a lower score of bleeding (0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels (P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammation cells, and massive fibrosis collagen depositions under the rectal wall, which revealed potential fibrosis formation. CONCLUSION: Diverting colostomy is a simple, effective and safe procedure for severe hemorrhagic CRP. Colostomy can improve quality of life and reduce serious complications secondary to radiotherapy. PMID:27350738

Sexually transmitted infections manifesting as proctitis

PubMed Central

Lamb, Chris A; Lamb, Elizabeth Iris Mary; Mansfield, John C; Sankar, K Nathan

2013-01-01

There is a rising incidence of several sexually transmitted infections (STIs), many of which can present with proctitis. Causative organisms include Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus, Treponema pallidum (syphilis), Giardia lamblia (giardiasis) and Entamoeba histolytica (amoebiasis). This paper outlines important clinical discriminators and key investigations to distinguish these organisms from non-infective pathology that include inflammatory bowel disease, solitary rectal ulcer syndrome and Behçet's syndrome. Management of these infections is described and suggestions are made for successful gastroenterology clinical consultation when an STI is suspected. PMID:23914292

High Dose-Rate Intracavitary Brachytherapy for Cervical Carcinomas With Lower Vaginal Infiltration

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

Kazumoto, Tomoko; Kato, Shingo; Tabushi, Katsuyoshi

2007-11-15

Purpose: This report presents the clinical applications of an automated treatment-planning program of high-dose-rate intracavitary brachytherapy (HDR-ICBT) for advanced uterine cervical cancer infiltrating the parametrium and the lower vagina. Methods and Materials: We adopted HDR-ICBT under optimized dose distribution for 22 cervical cancer patients with tumor infiltration of the lower half of the vagina. All patients had squamous cell carcinoma with International Federation of Gynecology and Obstetrics clinical stages IIB-IVA. After whole pelvic external beam irradiation with a median dose of 30.6 Gy, a conventional ICBT was applied as 'pear-shaped' isodose curve. Then 3-4 more sessions per week of thismore » new method of ICBT were performed. With a simple determination of the treatment volume, the cervix-parametrium, and the lower vagina were covered automatically and simultaneously by this program, that was designated as 'utero-vaginal brachytherapy'. The mean follow-up period was 87.4 months (range, 51.8-147.9 months). Results: Isodose curve for this program was 'galaxy-shaped'. Five-year local-progression-free survival and overall survival rates were 90.7% and 81.8%, respectively. Among those patients with late complications higher than Grade 2 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity score, only one (4.5%) developed severe proctitis. Conclusions: Because of the favorable treatment outcomes, this treatment-planning program with a simplified target-volume based dosimetry was proposed for cervical cancer with lower vaginal infiltration.« less

Prevalence of patient-reported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer.

PubMed

Tom, Ashlyn; Bennett, Antonia V; Rothenstein, Diana; Law, Ethel; Goodman, Karyn A

2018-01-01

Gastrointestinal (GI) symptoms pose a significant burden to patients receiving chemoradiation therapy (CRT) for anal cancer; however, the impact of symptoms from the patient perspective has not been quantified. This retrospective study examined and compared patient and clinician reports of acute GI toxicity during CRT. Patients treated with definitive RT using intensity-modulated radiation therapy for anal cancer between 9/09 and 11/12 were reviewed. Median RT dose was 56 Gy (range 45-56), and 76 patients (97%) received concurrent 5-fluorouracil-based chemotherapy. During RT, patients completed the 7-item Bowel Problem Scale (BPS) weekly. Clinicians assessed toxicity separately using CTCAE v. 3.0. Scores of BPS ≥ 3 and CTCAE ≥ 1 were considered to be clinically meaningful. Agreement of the two assessments was evaluated by Cohen's kappa coefficient. Seventy-eight patients completed at least one BPS and had a corresponding clinician assessment. Patients reporting scores of ≥3 was highest at week 5 (n = 68) for diarrhea (44.1%), proctitis (57.4%), and mucus (48.4%), while urgency (47.6%), tenesmus (31.7%), and cramping (27%) were highest at week 4 (n = 63). Baseline bleeding scores (26.7%; score ≥3) improved during treatment (13.4% at week 5). "Poor" agreement was observed between patient- and clinician-reported proctitis (Cohen's k = 0.11; n = 58); however, there was "good" agreement for diarrhea (Cohen's k = 0.68; n = 58). Acute GI toxicity during definitive CRT for anal cancer was most significant during weeks 4-5, while rectal bleeding improved during treatment. Discrepancies in patient- and clinician-reported symptoms demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments.

Clinical trial: a novel high-dose 1 g mesalamine suppository (Salofalk) once daily is as efficacious as a 500-mg suppository thrice daily in active ulcerative proctitis.

PubMed

Andus, Tilo; Kocjan, Andreas; Müser, Moritz; Baranovsky, Andrey; Mikhailova, Tatyana L; Zvyagintseva, Tatyana D; Dorofeyev, Andrey E; Lozynskyy, Yurii S; Cascorbi, Ingolf; Stolte, Manfred; Vieth, Michael; Dilger, Karin; Mohrbacher, Ralf; Greinwald, Roland

2010-11-01

Mesalamine suppositories are first-line therapy in active ulcerative proctitis; the standard regime still recommends multiple doses per day. The primary objective of this study was to show the noninferiority of once-daily administration of a novel 1 g mesalamine suppository versus thrice-daily administration of the 0.5 g mesalamine suppository. This was a single-blind (investigator-blinded), randomized, multicenter, comparative, Phase III clinical trial. Patients with mild to moderately active ulcerative proctitis inserted either one mesalamine 1 g suppository at bedtime or one mesalamine 0.5 g suppository thrice daily over a 6-week period. The primary endpoint was rate of remission (Disease Activity Index below 4). In all, 354 patients were evaluable for safety and per-protocol analysis. The new regimen demonstrated noninferiority: The percentage of patients with remission was 87.9% for the once-daily 1 g mesalamine suppository and 90.7% for the thrice-daily 0.5 g mesalamine suppository. Each regimen resulted in prompt cessation of clinical symptoms (e.g., median time to ≤3 stools per day (all without blood): 5 days in the 1 g mesalamine once-daily and 7 days in the 0.5 g mesalamine thrice-daily group). Patients preferred applying suppositories once a day. In active ulcerative proctitis the once-daily administration of a 1 g mesalamine suppository is as effective and safe, yet considerably more convenient, than the standard thrice-daily administration of a 0.5 g mesalamine suppository.

Lymphogranuloma Venereum 2015: Clinical Presentation, Diagnosis, and Treatment.

PubMed

Stoner, Bradley P; Cohen, Stephanie E

2015-12-15

Lymphogranuloma venereum (LGV) has emerged as an important cause of proctitis and proctocolitis in men who have sex with men; classical inguinal presentation is now increasingly uncommon. We report summary findings of an extensive literature review on LGV clinical presentation, diagnosis, and treatment that form the evidence base for the 2015 Centers for Disease Control and Prevention treatment guidelines for sexually transmitted diseases. Proctitis and proctocolitis are now the most commonly reported clinical manifestations of LGV, with symptoms resembling those of inflammatory bowel disease. Newer molecular tests to confirm LGV infection are sensitive and specific, but are generally restricted to research laboratory or public health settings. Doxycycline (100 mg twice daily for 21 days) remains the treatment of choice for LGV. Patients with rectal chlamydial infection and signs or symptoms of proctitis should be tested for LGV, or if confirmatory testing is not available, should be treated empirically with a recommended regimen to cover LGV infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Emerging role of thalidomide in the treatment of gastrointestinal bleeding.

PubMed

McFarlane, Michael; O'Flynn, Lauren; Ventre, Rachel; Disney, Benjamin R

2018-04-01

Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

Baseline Oral 5-ASA Use and Efficacy and Safety of Budesonide Foam in Patients with Ulcerative Proctitis and Ulcerative Proctosigmoiditis: Analysis of 2 Phase 3 Studies

PubMed Central

Sandborn, William J.; Rubin, David T.; Harper, Joseph R.

2016-01-01

Background: Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Methods: Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. Results: Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. Conclusions: Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423). PMID:27416045

Baseline Oral 5-ASA Use and Efficacy and Safety of Budesonide Foam in Patients with Ulcerative Proctitis and Ulcerative Proctosigmoiditis: Analysis of 2 Phase 3 Studies.

PubMed

Bosworth, Brian P; Sandborn, William J; Rubin, David T; Harper, Joseph R

2016-08-01

Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423).

Budesonide foam induces remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis.

PubMed

Sandborn, William J; Bosworth, Brian; Zakko, Salam; Gordon, Glenn L; Clemmons, David R; Golden, Pamela L; Rolleri, Robert L; Yu, Jing; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2015-04-01

Budesonide is a high-potency, second-generation corticosteroid designed to minimize systemic adverse consequences of conventional corticosteroids. We performed 2 randomized, phase 3 trials to evaluate the ability of budesonide rectal foam, formulated to optimize retention and provide uniform delivery of budesonide to the rectum and distal colon, to induce remission in patients with ulcerative proctitis or ulcerative proctosigmoiditis. Two identically designed, randomized, double-blind, placebo-controlled trials evaluated the efficacy of budesonide foam for induction of remission in 546 patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis who received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo. Remission at week 6 occurred significantly more frequently among patients receiving budesonide foam than placebo (Study 1: 38.3% vs 25.8%; P = .0324; Study 2: 44.0% vs 22.4%; P < .0001). A significantly greater percentage of patients receiving budesonide foam vs placebo achieved rectal bleeding resolution (Study 1: 46.6% vs 28.0%; P = .0022; Study 2: 50.0% vs 28.6%; P = .0002) and endoscopic improvement (Study 1: 55.6% vs 43.2%; P = .0486; Study 2: 56.0% vs 36.7%; P = .0013) at week 6. Most adverse events occurred at similar frequencies between groups, although events related to changes in cortisol values were reported more frequently with budesonide foam. There were no cases of clinically symptomatic adrenal insufficiency. Budesonide rectal foam was well tolerated and more efficacious than placebo in inducing remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. ClinicalTrials.gov ID: NCT01008410 and NCT01008423. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Benign Post-Radiation Rectal Stricture Treated with Endoscopic Balloon Dilation and Intralesional Triamcinolone Injection

PubMed Central

Karanikas, Michael; Touzopoulos, Panagiotis; Mitrakas, Alexandros; Zezos, Petros; Zarogoulidis, Paul; Machairiotis, Nikolaos; Efremidou, Eleni; Liratzopoulos, Nikolaos; Polychronidis, Alexandros; Kouklakis, George

2012-01-01

Post-radiation stricture is a rare complication after pelvis irradiation, but must be in the mind of the clinician evaluating a lower gastrointestinal obstruction. Endoscopy has gained an important role in chronic radiation proctitis with several therapeutic options for management of intestinal strictures. The treatment of rectal strictures has been limited to surgery with high morbidity and mortality. Therefore, a less invasive therapeutic approach for benign rectal strictures, endoscopic balloon dilation with or without intralesional steroid injection, has become a common treatment modality. We present a case of benign post-radiation rectal stricture treated successfully with balloon dilation and adjuvant intralesional triamcinolone injection. A 70-year-old woman presented to the emergency room complaining for 2 weeks of diarrhea and meteorism, 11 years after radiation of the pelvis due to adenocarcinoma of the uterus. Colonoscopy revealed a stricture at the rectum and multiple endoscopic biopsies were obtained from the stricture. The stricture was treated with endoscopic balloon dilation and intralesional triamcinolone injection. The procedure appears to have a high success rate and a very low complication rate. Histologic examination of the biopsies revealed non-specific inflammatory changes of the rectal mucosa and no specific changes of the mucosa due to radiation. All biopsies were negative for malignancy. The patient is stricture-free 12 months post-treatment. PMID:23271987

IRRADIATION PROCTITIS

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

Bishop, J.F.

1963-03-01

The incidence, pathology, symptoms, and treatment of radiation injury of the distal large bowel resulting from Ra or x-ray therapy of uterine cervical cancer are surveyed, and observations on 25 cases of irradiation proctitis are presented. In this series of patierts the incidence of significart rectal injury following irradiation of cervical cancer was approximates 10%. Each of the 25 women had symptoms sufficiently distressing so that the radiologist, gynecologist, or family doctor felt specialized care was needed. The histopathology of irradiation proctitis presented varying degrees of damage to the rectal epithelium. With severe injury, outright cell death occurred, whereas withmore » lesser involvemert, there were irregular areas of ulceration and a definite lag in the healing process. There were varying degrees of fibrosis and thickening of collagen and muscle fibers, which often resulted in loss of elasticity of the rectal wall, along with fixation of the mucosa to the underlying scar tissue and muscle. Gross pathology presented a variable picture. A few patients experienced first symptoms 3 to 4 months after the completion of treatment, but the largest group noticed the onset of difficulties from 6 to 9 months after trentment. Others had an even longer interval of a year or two, and three had no symptoms until between three and five years later. The symptoms varied with the severity of the involvement. Where rectal bleeding and tenesmus occurred and bowel damage was not excessive, ora1 steroids were of great value. Prednisone was used, beginning with 5 mg every 6 hr and increasing or decreasing in dosage in accordance with the response. As improvement occurred, the minimum maintenance dosage was sought, and when it was found it sometimes had to be continued for months. One patient needed 5 mg daily or on alternate days for 2 years, to prevent recurrence of bleeding. Hectal instillation of various therapeutic substances has been recommended but steroid suppositories, warm oil solutions of hydrocortizone, local anesthetics, and corn starch, all as retention medications, were tried and abandoned. Oral prednisone, along with nonnarcotic pain relief, and warm Sitz baths, seemed most effective. In some case however, the damage was so great that surgical relief was necessary. When the lesion was limited to the rectum, sigmoidal colostomy was the procedure of choice. (BBB)« less

Proctitis as the clinical presentation of lymphogranuloma venereum, a re-emerging disease in developed countries.

PubMed

López-Vicente, Jorge; Rodríguez-Alcalde, Daniel; Hernández-Villalba, Luis; Moreno-Sánchez, Diego; Lumbreras-Cabrera, Mercedes; Barros-Aguado, Carlos; Galán, Juan Carlos

2014-01-01

Lymphogranuloma venereum (LGV) is a sexually transmitted infectious disease caused by serovars L1, L2 and L3 of Chlamydia trachomatis. The initial presentation is usually a painless ulcerated papule on the genitalia or distal proctitis. The progression of the infection can lead to major complications: rectal strictures, intestinal obstruction or perforation. We present five cases of LGV proctitis as the initial presentation of the disease. All patients were male, mean age 44.6 years, with positive serology to human immunodeficiency virus (HIV) and promiscuous men who have sex with men (MSM).The initial diagnosis was made by rectosigmoidoscopy indicated for pain and anal discharge. All cases were confirmed by polymerase chain reaction technique in rectal tissue. Endoscopic images obtained showed a great variety of rectal lesions, from mild erythema of the mucosa and ulcers to deep ulcers with elevated borders and purulent exudate. All cases were resolved after treatment with doxycycline for 3 weeks. It emphasizes the importance of suspecting this re-emerging disease in patients with risk factors (HIV and MSM), with the aim of early treatment and to avoid major complications.

Californium-252 Brachytherapy Combined With External-Beam Radiotherapy for Cervical Cancer: Long-Term Treatment Results

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

Lei Xin; Qian Chengyuan; Qing Yi

Purpose: To observe, by retrospective analysis, the curative effects and complications due to californium-252 ({sup 252}Cf) neutron intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT) in the treatment of cervical cancer. Methods and Materials: From February 1999 to December 2007, 696 patients with cervical cancer (Stages IB to IIIB) were treated with {sup 252}Cf-ICBT in combination of EBRT. Of all, 31 patients were at Stage IB, 104 at IIA, 363 at IIB, 64 at IIIA, and 134 at IIIB. Californium-252 ICBT was delivered at 7-12 Gy per insertion per week, with a total dose of 29-45 Gy to reference pointmore » A in three to five insertions. The whole pelvic cavity was treated with 8-MV X-ray external irradiation at 2 Gy per fraction, four times per week. After 16-38 Gy of external irradiation, the center of the whole pelvic field was blocked with a 4-cm-wide lead shield, with a total external irradiation dose of 44-56 Gy. The total treatment course was 5 to 6 weeks. Results: Overall survival rate at 3 and 5 years for all patients was 76.0% and 64.9%, respectively. Disease-free 3- and 5-year survival rates of patients were 71.2% and 58.4%, respectively. Late complications included vaginal contracture and adhesion, radiation proctitis, radiation cystitis, and inflammatory bowel, which accounted for 5.8%, 7.1%, 6.2%, and 4.9%, respectively. Univariate analysis results showed significant correlation of stage, age, histopathologic grade, and lymph node status with overall survival. Cox multiple regression analysis showed that the independent variables were stage, histopathologic grade, tumor size, and lymphatic metastasis in all patients. Conclusion: Results of this series suggest that the combined use of {sup 252}Cf-ICBT with EBRT is an effective method for treatment of cervical cancer.« less

Can a peri-rectal hydrogel spaceOAR programme for prostate cancer intensity-modulated radiotherapy be successfully implemented in a regional setting?

PubMed

Te Velde, Bridget L; Westhuyzen, Justin; Awad, Nader; Wood, Maree; Shakespeare, Thomas P

2017-08-01

The aim of this study was to investigate whether the implementation of a hydrogel spacer (SpaceOAR) programme for patients treated with 81 Gy prostate intensity-modulated radiotherapy (IMRT) in a regional setting can reduce rectal doses and toxicity. In this retrospective study, 125 patients with localised prostate cancer treated between April 2014 (programme commencement) and June 2015 were compared: 65 with SpaceOAR (inserted by five different urologists) and 60 patients treated over the same time period without SpaceOAR. Patients were treated with 81 Gy in 45Fx of IMRT over 9 weeks. Planning aims included restricting rectal doses to V40 Gy < 35%, V65 Gy < 17%, V75 Gy < 10%. Acute toxicity was assessed weekly during radiotherapy and at 12 weeks. Rectal volume parameters were all significantly lower in the SpaceOAR group, with an associated reduction in acute diarrhoea (13.8% vs 31.7%). There were no significant differences in the very low rates of acute and late faecal incontinence or proctitis, however, there was a trend towards increased haemorrhoid rate in the SpaceOAR group (11.7% vs 3.1%, P = 0.09). A SpaceOAR programme in a regional setting with urologists performing low volumes of insertions (<1 per month on average) is of clinical benefit, and was associated with significantly lower radiation doses to the rectum and lower rates of acute diarrhoea. © 2017 The Royal Australian and New Zealand College of Radiologists.

Successful treatment for ulcerative proctitis with rectal tacrolimus in an 8-year-old girl with intolerance to mesalamine.

PubMed

Navas-López, Víctor Manuel; Blasco-Alonso, Javier; Girón Fernández-Crehuet, Francisco; Serrano Nieto, Maria Juliana; Gallego-Gutiérrez, Silvia; Luque Pérez, Silvia; Sierra Salinas, Carlos

2014-08-01

Ulcerative colitis (UC) is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granulomas on biopsy. It affects the rectum, and, to a variable extent, the colon in continuity and is characterized by a relapsing and remitting course. Oral 5-aminosalicylic acid (5-ASA) regimens are recommended as first-line induction therapy for mild to moderately active pediatric UC and for maintenance of remission regardless of other initial treatments. In large clinical trials in adults, mesalamine intolerance was found in 2-5 % of the patients. We present a case of an 8-year-old female patient with intolerance to mesalamine and proctitis resistant to conventional therapy who responded to rectal tacrolimus treatment. The patient started with a dose of 2 mg/day at night with an excellent response. She reported feeling better than any of the previously prescribed treatments and without feeling the discomfort of previously administered enemas. After four weeks of treatment, the dose was reduced to 2 mg/week with no relapses. Tacrolimus suppositories were very well tolerated, and no adverse effects have been reported. Although only very little data has been published, rectal tacrolimus seems to be safe and of efficacy in ulcerative proctitis resistant to standard therapy.

Anorectal Lymphogranuloma Venereum in Madrid: A Persistent Emerging Problem in Men Who Have Sex With Men.

PubMed

Cabello Úbeda, Alfonso; Fernández Roblas, Ricardo; García Delgado, Rosa; Martínez García, Laura; Sterlin, Fabiola; Fernández Guerrero, Manuel L; Górgolas, Miguel

2016-07-01

Since 2003, outbreaks of lymphogranuloma venereum (LGV) with anorectal syndrome have been increasingly recognized in many Western countries. All of them have been classified as LGV serovar L2b, mainly occurring in human immunodeficiency virus (HIV)-infected men who have had sex with men (MSM). We describe a series of 26 diagnosed cases of LGV proctitis in downtown Madrid, Spain, in 2014, after implementing routine diagnostic procedures for this disease in symptomatic MSM. We conducted an observational study of patients with symptomatic proctitis attending an outpatient infectious diseases clinic in Madrid, Spain during calendar year 2014. Clinical, epidemiological, laboratory, and therapeutic data were gathered and analyzed. Twenty-six patients were included in the analysis. All were MSM, and 24 of them were HIV-positive. All patients reported having acute proctitis symptoms including tenesmus (85%), pain (88%), constipation (62%), or anal discharge (96%). Proctoscopy showed mucopurulent exudate (25 patients [96%]), and rectal bleeding, with mucosal erythema and/or oedema in all cases. Rectal swabs were obtained from all patients, and LGV serovar L2 was confirmed in all of them. The cure rate was 100% after standard treatments with doxycycline 100 mg twice per day for 3 weeks. Simultaneous rectal infections with other sexually transmitted pathogens (gonorrhoea, herpes simplex virus, Mycoplasma genitalium) and systemic sexually transmitted diseases (STDs) (syphilis, acute HIV, and hepatitis C infections) were also documented in 12 patients (46%), but these co-infections did not appear to influence the clinical manifestations of LGV. Anorectal LGV is a common cause of acute proctitis and proctocolitis among HIV-infected MSM who practice unprotected anal sex, and it is frequently associated with other rectal STDs. The implementation of routine screening and prompt diagnosis of these rectal infections should be mandatory in all clinical settings attended by HIV and STD patients.

Endomicroscopy for assessing mucosal healing in patients with ulcerative colitis.

PubMed

Gheorghe, Cristian; Cotruta, Bogdan; Iacob, Razvan; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Liana

2011-12-01

The assessment of tissue healing has emerged as an important treatment goal in patients with inflammatory bowel disease. In patients with ulcerative colitis (UC), mucosal healing may represent the ultimate therapeutic goal due to the fact that the inflammation is limited to the mucosal layer. Mucosal and histological healing may indicate a subset of UC patients in long-term clinical, endoscopic and histological remission in whom immunomodulators, biologics, and even aminosalicylates may be withdrawn. Confocal laser endomicroscopy allows the assessment of residual cellular inflammation, crypt and vessel architecture distortion during ongoing endoscopy, and therefore permits a real-time evaluation of histological healing in patients with ulcerative proctitis. Images of conventional optical microscopy and confocal laser endomicroscopy in patients with ulcerative proctitis in remission are presented.

Double-blind, placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using /sup 99m/Tc-labeled 5-ASA suppositories

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

Williams, C.N.; Haber, G.; Aquino, J.A.

1987-12-01

Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500 mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0-3. There was thus 0-12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients,more » with initial mean DAI 7.1 +/- 1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1 +/- 1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given /sup 99m/Tc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis.« less

Hydrocortisone Rectal

MedlinePlus

Rectal hydrocortisone is used along with other medications to treat proctitis (swelling in the rectum) and ulcerative colitis (a ... and swelling from hemorrhoids and other rectal problems. Hydrocortisone is in a class of medications called corticosteroids. ...

XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

PubMed

Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

2014-03-01

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

76 FR 72952 - Guidance for Industry on Nonclinical Evaluation of Late Radiation Toxicity of Therapeutic...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... effects of therapeutic radiopharmaceutical agents. This guidance is not intended to address late radiation... and is often self-limiting and reversible. In contrast, late radiation toxicity (e.g., renal failure...

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

NASA Astrophysics Data System (ADS)

Herrera, Higmar; Yañez, Elvia; Deras, Diana C.; Reyes, Francianella

2010-12-01

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55±13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

Lymphogranuloma venereum: an old, forgotten re-emerging systemic disease.

PubMed

Dal Conte, I; Mistrangelo, M; Cariti, C; Chiriotto, M; Lucchini, A; Vigna, M; Morino, M; Di Perri, G

2014-03-01

Lymphogranuloma venereum (LGV) is a sexually transmitted infection endemic in parts of Africa, Asia, South America, and the Caribbean, but once was rarely observed in Western countries, where most cases were considered to be imported. However, recent outbreaks have been reported in Europe, Australia, New Zealand, the United States and Canada, mainly among HIV positive men who have sex with men, signaling LGV re-emergence. The etiological agent of LGV is Chlamydia trachomatis serotypes L1, L2 and L3, and current outbreaks are mostly sustained by L2b type. The clinical course can be classically divided into three stages: an initial papule, which may ulcerate at the site of inoculation, followed by regional lymphoadenopathy (second stage, generally unilateral). In the tertiary stage, lymphatic obstruction, with elephantiasis of genitalia, and rectal involvement can lead to the formation of strictures and fistulae that may require surgical treatment. Recent cases are observed mainly among HIV positive people, often co-infected with HCV and others STIs, engaging in high-risk sexual practices. The main clinical picture is a relative new entity characterized by progressive ulcerative proctitis, the so called anorectal syndrome. Diagnosis is often delayed, requires a high index of clinical suspicion and must rely on the use of nucleic acid amplification tests. The differential diagnosis of proctitis should include LGV infection. Gastroenterologists, coloproctologists, dermatologists and other specialists need to be aware of LGV proctitis to avoid diagnostic delay and progression of disease to the tertiary stage.

Lymphogranuloma venereum proctitis: a differential diagnose to inflammatory bowel disease.

PubMed

Høie, Sverre; Knudsen, Lene Surland; Gerstoft, Jan

2011-04-01

Lymphogranuloma venereum (LGV) is a sexually transmitted disease, endemic in tropical and subtropical areas for many years. After 2003 there have been several outbreaks in western countries, especially among HIV-positive men who have sex with men (MSM). An important manifestation of LGV is a proctitis, with a clinical presentation and endoscopic findings resembling those of inflammatory bowel diseases (IBDs). LGV is considered new in Scandinavia. This case report focuses on difficulties in differentiating LGV and IBD. This case report used a systematic search in the literature using PubMed and clinical cases from the Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark (Cases 1-3) and the Section of Surgery, Hamar Hospital, Norway (Case 4). Clinical and endoscopic findings in LGV and IBD resemble each other. All cases were MSM. Three out of four were HIV-positive. Three out of four contacted their general practitioner (GP) due to gastrointestinal (GI) symptoms, and were referred to a gastroenterologist (GE) with suspicion of IBD. Because of non-successful IBD treatment, control of HIV status, relapses of GI-symptoms or extended information concerning sexual habits, LGV was suspected and diagnosed. All patients responded with remission of GI-symptoms and endoscopic findings after oral treatment with doxycycline. Due to similarities between LGV and IBD, LGV should be considered as a differential diagnosis in patients with proctitis or IBD-related symptoms, especially among HIV-positive men. Hence LGV patients may be spared long-lasting examination, mistreatment and surgery.

Outpatient application of formalin for chronic rectal bleeding after prostate irradiation: a quasi-experimental study.

PubMed

Viani, Gustavo Arruda; Sakamoto, Aline

2017-07-01

The aim of this quasi-experimental study is to evaluate a novel technique for an outpatient application of formalin for chronic rectal bleeding after prostate irradiation. This is a quasi- experimental clinical trial developed between January 2010 and July 2015, including 35 patients with chronic radiation rectitis (CRP) due to a previous prostate radiation course. The study's eligibility was (1) completed external beam radiation therapy for prostate carcinoma >6 months previously, (2) rectal bleeding, defined as a frequency of >1× per week and/or needing of blood transfusions, and (3) diagnosis of chronic proctitis at colonoscopy. The 5% formalin application was performed by a custom applicator, which requires neither anesthesia nor sigmoidoscopy. The endpoint of the study was bleeding cessation and hemoglobin level. The onset of bleeding due to chronic rectitis was 12 months (6-36). During a median follow-up of 24 months, the rate of overall efficacy was 94%. The sustained complete response in 1 and 2 years was 80% and 73%, respectively. The Hb mean pre- and post-treatment differed significantly (12.2 vs 14.4, p = 0.0001). The rates of blood transfusion differed significantly, pre- and post-treatment (17% vs 5.7%, p = 0.031). The technique is very effective and safe, resulting to a significant improvement of hemoglobin levels and quality of life scores. Further studies are warranted to compare this technique with other treatment options for chronic radiation-induced rectal bleeding.

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

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

Herrera, Higmar; Yanez, Elvia; Deras, Diana C.

2010-12-07

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher agemore » (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).« less

Ulcerative proctitis: a review of pharmacotherapy and management.

PubMed

Lakatos, Peter Laszlo; Lakatos, Laszlo

2008-04-01

Ulcerative proctitis (UP) is a common presentation of ulcerative colitis (UC). To summarize available literature on up-to-date management and pharmacotherapy of UP patients. Extensive Medline/Embase literature search was performed to identify relevant articles. Topical medication with rectally administered 5-aminosalicylic acid (5-ASA)/corticosteroid suppositories or enemas is effective treatment for most UP patients. Locally administered 5-ASA is more efficacious than oral compounds. The combination of topical 5-ASA and oral 5-ASA or topical steroids should be considered for escalation of treatment. Maintenance treatment is indicated in all UC cases. 5-ASA suppositories are suggested as first-line maintenance therapy if accepted by patients, although oral 5-ASA as maintenance therapy might prevent proximal extension of the disease. After re-assessment, chronically active patients refractory or intolerant to 5-ASAs and corticosteroids may require immunomodulators or biological therapy. Exceptional cases may require a proctocolectomy.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.

PubMed

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; Ruiz de Almodóvar, José Mariano

2005-01-01

Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.

Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity in prostate cancer patients.

PubMed

Schnarr, Kara; Boreham, Douglas; Sathya, Jinka; Julian, Jim; Dayes, Ian S

2009-08-01

To examine a potential correlation between the in vitro apoptotic response of lymphocytes to radiation and the risk of developing late gastrointestinal (GI)/genitourinary (GU) toxicity from radiotherapy for prostate cancer. Prostate cancer patients formerly enrolled in a randomized study were tested for radiosensitivity by using a radiation-induced lymphocyte apoptosis assay. Apoptosis was measured using flow cytometry-based Annexin-FITC/7AAD and DiOC(6)/7AAD assays in subpopulations of lymphocytes (total lymphocytes, CD4+, CD8+ and CD4-/CD8-) after exposure to an in vitro dose of 0, 2, 4, or 8 Gy. Patients with late toxicity after radiotherapy showed lower lymphocyte apoptotic responses to 8 Gy than patients who had not developed late toxicity (p = 0.01). All patients with late toxicity had apoptosis levels that were at or below the group mean. The negative predictive value in both apoptosis assays ranged from 95% to 100%, with sensitivity values of 83% to 100%. Apoptosis at lower dose points and in lymphocyte subpopulations had a weaker correlation with the occurrence of late toxicity. Lymphocyte apoptosis after 8 Gy of radiation has the potential to predict which patients will be spared late toxicity after radiation therapy. Further research should be performed to identify the specific subset of lymphocytes that correlates with late toxicity, followed by a corresponding prospective study.

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

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

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng

2013-11-01

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays,more » were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.« less

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

PubMed Central

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; de Almodóvar, José Mariano Ruiz

2005-01-01

Introduction Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Methods Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Results Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. Conclusion After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients. PMID:16168114

Assessing correlations between the spatial distribution of the dose to the rectal wall and late rectal toxicity after prostate radiotherapy: an analysis of data from the MRC RT01 trial (ISRCTN 47772397)

NASA Astrophysics Data System (ADS)

Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Sydes, Matthew R.; Dearnaley, David P.; Partridge, Mike

2009-11-01

Many studies have been performed to assess correlations between measures derived from dose-volume histograms and late rectal toxicities for radiotherapy of prostate cancer. The purpose of this study was to quantify correlations between measures describing the shape and location of the dose distribution and different outcomes. The dose to the rectal wall was projected on a two-dimensional map. In order to characterize the dose distribution, its centre of mass, longitudinal and lateral extent, and eccentricity were calculated at different dose levels. Furthermore, the dose-surface histogram (DSH) was determined. Correlations between these measures and seven clinically relevant rectal-toxicity endpoints were quantified by maximally selected standardized Wilcoxon rank statistics. The analysis was performed using data from the RT01 prostate radiotherapy trial. For some endpoints, the shape of the dose distribution is more strongly correlated with the outcome than simple DSHs. Rectal bleeding was most strongly correlated with the lateral extent of the dose distribution. For loose stools, the strongest correlations were found for longitudinal extent; proctitis was most strongly correlated with DSH. For the other endpoints no statistically significant correlations could be found. The strengths of the correlations between the shape of the dose distribution and outcome differed considerably between the different endpoints. Due to these significant correlations, it is desirable to use shape-based tools in order to assess the quality of a dose distribution.

Impact of late radiation effects on cancer survivor children: an integrative review

PubMed Central

Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia

2016-01-01

ABSTRACT We aimed to identify the late effects of radiation exposure in pediatric cancer survivors. An integrated literature review was performed in the databases MEDLINE and LILACS and SciELO. Included were articles in Portuguese and English, published over the past 10 years, using the following keywords: “neoplasias/neoplasms” AND “radioterapia/radiotherapy” AND “radiação/radiation”. After analysis, 14 articles - published in nine well-known journals - met the inclusion criteria. The publications were divided into two categories: “Late endocrine effects” and “Late non-endocrine effects”. Considering the increased survival rates in children who had cancer, the impact of late effects of exposure to radiation during radiological examinations for diagnosis and treatment was analyzed. Childhood cancer survivors were exposed to several late effects and should be early and regularly followed up, even when exposed to low radiation doses. PMID:26313432

Outcomes After Intensity-Modulated Versus Conformal Radiotherapy in Older Men With Nonmetastatic Prostate Cancer

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

Bekelman, Justin E., E-mail: bekelman@uphs.upenn.edu; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA

Purpose: There is little evidence comparing complications after intensity-modulated (IMRT) vs. three-dimensional conformal radiotherapy (CRT) for prostate cancer. The study objective was to test the hypothesis that IMRT, compared with CRT, is associated with a reduction in bowel, urinary, and erectile complications in elderly men with nonmetastatic prostate cancer. Methods and Materials: We undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. We identified men aged 65 years or older diagnosed with nonmetastatic prostate cancer in the United States between 2002 and 2004 who received IMRT (n = 5,845) or CRT (n = 6,753).more » The primary outcome was a composite measure of bowel complications. Secondary outcomes were composite measures of urinary and erectile complications. We also examined specific subsets of bowel (proctitis/hemorrhage) and urinary (cystitis/hematuria) events within the composite complication measures. Results: IMRT was associated with reductions in composite bowel complications (24-month cumulative incidence 18.8% vs. 22.5%; hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.79-0.93) and proctitis/hemorrhage (HR 0.78; 95% CI, 0.64-0.95). IMRT was not associated with rates of composite urinary complications (HR 0.93; 95% CI, 0.83-1.04) or cystitis/hematuria (HR 0.94; 95% CI, 0.83-1.07). The incidence of erectile complications involving invasive procedures was low and did not differ significantly between groups, although IMRT was associated with an increase in new diagnoses of impotence (HR 1.27, 95% CI, 1.14-1.42). Conclusion: IMRT is associated with a small reduction in composite bowel complications and proctitis/hemorrhage compared with CRT in elderly men with nonmetastatic prostate cancer.« less

Acute Toxicity of Radiochemotherapy in Rectal Cancer Patients: A Risk Particularly for Carriers of the TGFB1 Pro25 variant

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

Schirmer, Markus Anton; Mergler, Caroline Patricia Nadine; Rave-Fraenk, Margret

Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions. Methods and Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade {>=}2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germlinemore » polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped. Results: In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT. Conclusion: The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques.« less

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

PubMed Central

Zeidan, Youssef H.; Xiao, Nan; Cao, Hongbin; Kong, Christina; Le, Quynh-Thu; Sirjani, Davud

2016-01-01

Purpose Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage. Methods and Materials We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment. Results Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation. Conclusions These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of xerostomia in patients with head and neck cancer. PMID:26907915

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

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

Zeidan, Youssef H., E-mail: zeidan@miami.edu; Xiao, Nan; Cao, Hongbin

Purpose: Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage. Methods and Materials: We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hoursmore » before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment. Results: Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation. Conclusions: These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of xerostomia in patients with head and neck cancer.« less

Ulcerative Colitis and Crohn's Disease: Implications for College Health Programs

ERIC Educational Resources Information Center

Gelphi, A. P.

1977-01-01

The author reviews clinical patterns of inflammatory bowel disorders, establishes a perspective for recognizing ulcerative colitis, ulcerative proctitis, and Crohn's disease in relation to other bowel inflammations, and suggests some epidemiologic strategies for studying etiology, pathogenesis, and natural history of the diseases. (MJB)

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Late complications of pelvic irradiation in 16 dogs.

PubMed

Anderson, Christine R; McNiel, Elizabeth A; Gillette, Edward L; Powers, Barbara E; LaRue, Susan M

2002-01-01

When external beam radiation therapy is administered to the pelvis, normal tissues irradiated may include the colon, small intestine, urethra, bladder, bone, and spinal cord. The objectives of this retrospective study were to determine the incidence and severity of late radiation effects following pelvic irradiation in dogs and to identify factors that increase the risk of these effects. Medical records of all dogs treated with curative intent external beam radiation therapy to the pelvic region between 1993 and 1999 were reviewed. Patients with follow-up longer than 9 months or any patient that developed late complications earlier than 9 months were evaluated. Sixteen dogs met criteria for inclusion in this study. All dogs were treated with a 6-MV linear accelerator with bilaterally opposed beams. Diseases treated included transitional cell carcinoma of the bladder, transitional cell carcinoma of the prostate, and anal sac apocrine gland adenocarcinoma. Four dose/fractionation schemes were used: 49.5 Gy in 3.3 Gy fractions, 54 Gy in 3.0 Gy fractions, 54 Gy in 2.7 Gy fractions, and 18 Gy intraoperative radiation therapy followed by 43 Gy external beam radiation therapy in 2.9 Gy fractions. Implantable chemotherapy in the form of an OPLA-Pt sponge was used in six dogs as a radiation potentiator. Colitis was the major late effect following pelvic irradiation, occurring in nine dogs (56%). Colitis was characterized as mild in three dogs, moderate in one dog, and severe in five dogs. Three of the dogs with severe effects suffered gastrointestinal perforation. All dogs with severe late effects received 3 or 3.3 Gy per fraction, and 80% received radiation potentiators. In the seven dogs that received 2.7 Gy or 2.9 Gy per fraction, late effects were classified as none (n = 5), mild colitis (n = 1), and moderate colitis (n = 1). Radiation therapy can be administered to the pelvic region with a minimal risk of late effects to the colon by giving smaller doses per fraction and avoiding systemic radiation potentiators.

Bubonic lymphogranuloma venereum with multidrug treatment failure.

PubMed

Vall-Mayans, Martí; Isaksson, Jenny; Caballero, Estrella; Sallés, Beatriz; Herrmann, Björn

2014-03-01

A patient with proctitis and inguinal buboes diagnosed with lymphogranuloma venereum (LGV) was treated with doxycycline 21 days, azithromycin 20 days and moxifloxacin for a further 12 days because of progressive worsening of inguinal symptoms. Despite extensive antibiotic treatment, the inguinal LGV lesions persisted; however, the patient recovered spontaneously after three months.

[Hematopoiesis during remote period after acute radiation syndrome].

PubMed

Kotenko, K V; Bushmanov, A Iu; Suvorova, L A; Galstian, I A; Nadezhina, N M; Nugis, V Iu

2011-01-01

Based on the long (19.7 +/- 1.8 year) hemopoiesis follow-up study in 152 patients after acute radiation syndrome (ARS) as a result of exposure to gamma-, gamma-beta and gamma-eta radiation in a wide dose range (1.2-9.8 Gy) it was detected that cytopenia appears in the late consequences period: thrombocytopenia was found in 26.9% cases, leukocytopenia, neutropenia and lymphocytopenia--in 13.1% patients. A higher ARS degree causes the increase of various disorders (cytopenia and cytosis) in the late period. It reflects a tight interrelation between blood cell contents and radiation dose. Frequency of cytopenias increases if such somatic disorders: persistent hepatitis, hepatic cirrhosis and late radiation ulcers as appear.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

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

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment.« less

Chlamydia trachomatis in Cervical Lymph Node of Man with Lymphogranuloma Venereum, Croatia, 20141.

PubMed

Gjurašin, Branimir; Lepej, Snježana Židovec; Cole, Michelle J; Pitt, Rachel; Begovac, Josip

2018-04-01

We report an HIV-infected person who was treated for lymphogranuloma venereum cervical lymphadenopathy and proctitis in Croatia in 2014. Infection with a variant L2b genovar of Chlamydia trachomatis was detected in a cervical lymph node aspirate. A prolonged course of doxycycline was required to cure the infection.

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

Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi

Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicitymore » was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the possibility of such ethnic heterogeneity in the late toxicities of radiation.« less

Do no harm--normal tissue effects

NASA Technical Reports Server (NTRS)

Hall, E. J.

2001-01-01

Radiation therapy confers enormous benefits that must be balanced against the possibilities for harm including late toxicity in normal tissues and radiation-induced second malignancies. A small percentage of patients experience severe late complications. The question is, do these late sequelae occur randomly, or are they confined to individuals who are genetically predisposed to radiosensitivity. Experiments with knockout mice and with patients demonstrate that individuals heterozygous for a number of genes appear to be radiosensitive. If radiosensitive patients were identified prospectively by genetic analysis, they could be spared the trauma of late sequelae. Several large studies have shown a statistically significant excess of radiation-induced malignancies in radiotherapy patients. Most second cancers are carcinomas, developing in the lining cells of the body often remote from the treatment site. Radiation-induced sarcomas appear only in the heavily irradiated areas. These are small in number but appear with a very high relative risk.

Long-term hepatic outcomes in survivors of stage 4S and 4 neuroblastoma in infancy.

PubMed

French, Amy E; Irwin, Meredith S; Navarro, Oscar M; Greenberg, Mark; Nathan, Paul C

2012-02-01

Infants with stage 4 and 4S neuroblastoma (NB) have a superior prognosis to older children. However, they often require intensive therapy including abdominal radiation. We aimed to investigate the long-term hepatic outcomes in infants with stage 4S and 4 NB. We reviewed the charts of 38 infants diagnosed with stage 4S and 4 NB between 1984 and 2002. We included only those with available follow-up 5 years following diagnosis. We assessed hepatic imaging and function (transaminases, bilirubin, alkaline phosphatase) at all available time points from diagnosis. Abnormalities present at more than 5 years from diagnosis were considered persistent late changes. We identified 15 stage 4S and 12 stage 4 patients. Twelve of 15 stage 4S patients had hepatic involvement at diagnosis, 8 of whom required abdominal radiation. Five of eight demonstrated late imaging changes. Two of four with hepatic metastases but no radiation demonstrated late imaging changes. The late imaging changes resolved over time and without intervention in 3/7 survivors. The persistent lesions included liver fibrosis (1) and focal nodular hyperplasia (FNH) (3). Five of 12 stage 4 NB patients had hepatic involvement at diagnosis; none required radiation or had late hepatic imaging changes. In stage 4S NB, adverse hepatic effects are infrequent, may resolve over time, and occur with or without radiation. FNH should be considered in those with persistent late imaging changes. Adverse hepatic outcomes after liver involvement or radiation in infants with stage 4 NB rarely occur. Copyright © 2011 Wiley Periodicals, Inc.

Chlamydia trachomatis in Cervical Lymph Node of Man with Lymphogranuloma Venereum, Croatia, 20141

PubMed Central

Lepej, Snježana Židovec; Cole, Michelle J.; Pitt, Rachel; Begovac, Josip

2018-01-01

We report an HIV-infected person who was treated for lymphogranuloma venereum cervical lymphadenopathy and proctitis in Croatia in 2014. Infection with a variant L2b genovar of Chlamydia trachomatis was detected in a cervical lymph node aspirate. A prolonged course of doxycycline was required to cure the infection. PMID:29553338

Development of quantitative parameters to assess in-vivo optical coherence tomography images of late oral radiation toxicity patients

NASA Astrophysics Data System (ADS)

Davoudi, Bahar; Damodaran, Vani; Bizheva, Kostadinka; Yang, Victor; Dinniwell, Robert; Levin, Wilfred; Vitkin, Alex

2013-03-01

Late oral radiation toxicity is a common condition occurring in a considerable percentage of head and neck cancer patients after radiation therapy which reduces their quality of life. The current examination of these patients is based on a visual inspection of the surface of the oral cavity; however, it is well known that many of the complications start in the subsurface layers before any superficial manifestation. Considering the currently suboptimal examination techniques, we address this clinical problem by using optical coherence tomography (OCT) to monitor the subsurface oral layers with micron-scale resolution images. A spectral-domain OCT system and a specialized oral imaging probe were designed and built for a clinical study to image late oral radiation toxicity patients. In addition to providing qualitative 2D and 3D images of the subsurface oral layers, quantitative metrics were developed to assess the back-scattering and thickness properties of different layers. Metric derivations are explained and preliminary results from late radiation toxicity patients and healthy volunteers are presented and discussed.

Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

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

Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca; Fortin, Andre; Wang, Chang Shu

2012-03-15

Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, andmore » the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help tailoring therapies to reduce toxicities among patients treated with RT for HNC.« less

Two-year follow-up after intracoronary gamma radiation therapy.

PubMed

Condado, J A; Waksman, R; Calderas, C; Saucedo, J; Lansky, A

1999-01-01

Neointimal hyperplasia and unfavorable remodeling have been demonstrated to be the major limitation to endovascular revascularization procedures. Intracoronary gamma radiation therapy has been shown to reduce the restenosis index. However, the late effects of these novel procedures are unknown. To evaluate the long-term effects on clinical and angiographic outcome of endovascular gamma radiation therapy following percutaneous transluminal coronary angioplasty (PTCA), serial angiography over a 2-year period was performed in 21 patients (22 lesions) who were treated with 192Ir in doses of 20-25 Gy after PTCA. Angiograms were analyzed using quantitative methods (QCA). The mean late loss between PTCA and 6 months was 0.20 +/- 0.59 and 0.13 +/- 0.84 between 6 months and 2 years. At 6 months, angiographic binary restenosis was present in six arteries (27.2%). At 2 years, binary restenosis was observed in six arteries (27.2%), including one patient who had developed restenosis and excluding one patient with spontaneous regression. Two early pseudoaneurysms and two late aneurysms were observed at 6 months, with little increase at 2 years. No other angiographic complication was observed. None of the patients or medical staff developed complications or illnesses that could be related to the effects of the radiation procedure. Gamma radiation therapy decreases late luminal loss, is safe and free of unexpected complications at 6 months follow-up, with no significant changes or late complications at 2-years' follow-up.

Late Infection-Related Mortality in Asplenic Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

PubMed

Weil, Brent R; Madenci, Arin L; Liu, Qi; Howell, Rebecca M; Gibson, Todd M; Yasui, Yutaka; Neglia, Joseph P; Leisenring, Wendy M; Smith, Susan A; Tonorezos, Emily S; Friedman, Danielle N; Constine, Louis S; Tinkle, Christopher L; Diller, Lisa R; Armstrong, Gregory T; Oeffinger, Kevin C; Weldon, Christopher B

2018-06-01

Purpose Infection-related outcomes associated with asplenia or impaired splenic function in survivors of childhood cancer remains understudied. Methods Late infection-related mortality was evaluated in 20,026 5-year survivors of childhood cancer (diagnosed < 21 years of age from 1970 to 1999; median age at diagnosis, 7.0 years [range, 0 to 20 years]; median follow-up, 26 years [range, 5 to 44 years]) using cumulative incidence and piecewise-exponential regression models to estimate adjusted relative rates (RRs). Splenic radiation was approximated using average dose (direct and/or indirect) to the left upper quadrant of the abdomen (hereafter, referred to as splenic radiation). Results Within 5 years of diagnosis, 1,354 survivors (6.8%) had a splenectomy and 9,442 (46%) had splenic radiation without splenectomy. With 62 deaths, the cumulative incidence of infection-related late mortality was 1.5% (95% CI, 0.7% to 2.2%) at 35 years after splenectomy and 0.6% (95% CI, 0.4% to 0.8%) after splenic radiation. Splenectomy (RR, 7.7; 95% CI, 3.1 to 19.1) was independently associated with late infection-related mortality. Splenic radiation was associated with increasing risk for late infection-related mortality in a dose-response relationship (0.1 to 9.9 Gy: RR, 2.0; 95% CI, 0.9 to 4.5; 10 to 19.9 Gy: RR, 5.5; 95% CI, 1.9 to 15.4; ≥ 20 Gy: RR, 6.0; 95% CI, 1.8 to 20.2). High-dose alkylator chemotherapy exposure was also independently associated with an increased risk of infection-related mortality (RR, 1.9; 95% CI, 1.1 to 3.4). Conclusion Splenectomy and splenic radiation significantly increase risk for late infection-related mortality. Even low- to intermediate-dose radiation exposure confers increased risk, suggesting that the spleen is highly radiosensitive. These findings should inform long-term follow-up guidelines for survivors of childhood cancer and should lead clinicians to avoid or reduce radiation exposure involving the spleen whenever possible.

Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

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

Corn, Paul G., E-mail: pcorn@mdanderson.org; Song, Danny Y.; Heath, Elisabeth

Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles).more » A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.« less

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

Not Available

Complete texts of 123 communications to the Congress (in the original language; the majority in English, some in Russian, French), on the following topics; radiation perspective in the U.S., radiation and man, non-ionising radiation, radiation effects on animals, radiation quantities, radioecology, reactor experience, late radiation effects, dose calculations and radiation accidents.

Fractionation Spares Mice From Radiation-Induced Reductions in Weight Gain But Does Not Prevent Late Oligodendrocyte Lineage Side Effects

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

Begolly, Sage; Shrager, Peter G.; Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York

Purpose: To determine the late effects of fractionated versus single-dose cranial radiation on murine white matter. Methods and Materials: Mice were exposed to 0 Gy, 6 × 6 Gy, or 1 × 20 Gy cranial irradiation at 10 to 12 weeks of age. Endpoints were assessed through 18 months from exposure using immunohistochemistry, electron microscopy, and electrophysiology. Results: Weight gain was temporarily reduced after irradiation; greater loss was seen after single versus fractionated doses. Oligodendrocyte progenitor cells were reduced early and late after both single and fractionated irradiation. Both protocols also increased myelin g-ratio, reduced the number of nodes of Ranvier, and promoted a shift in the proportion of small, unmyelinatedmore » versus large, myelinated axon fibers. Conclusions: Fractionation does not adequately spare normal white matter from late radiation side effects.« less

Late radiation responses in man: Current evaluation from results from Hiroshima and Nagasaki

NASA Astrophysics Data System (ADS)

Schull, William J.

Among the late effects of exposure to the atomic bombings of Hiroshima and Nagasaki, none looms larger than radiation related malignancies. Indeed, the late effects of A-bomb radiation on mortality appear to be limited to an increase in malignant tumors. At present, it can be shown that cancers of the breast, colon, esophagus, lungs, stomach, thyroid, and urinary tract as well as leukemia and multiple myeloma increase in frequency with an increase in exposure. No significant relationship to radiation can as yet be established for malignant lymphoma, nor cancers of the rectum, pancreas or uterus. Radiation induced malignancies other than leukemia seem to develop proportionally to the natural cancer rate for the attained age. For specific age-at-death intervals, both relative and absolute risks tend to be higher for those of younger age at the time of bombing. Other late effects include radiation-related lenticular opacities, disturbances of growth among those survivors still growing at the time of exposure, and mental retardation and small head sizes among the in utero exposed. Chromosomal abnormalities too are more frequently encountered in the peripheral leucocytes of survivors, and this increase is functionally related to their exposure. Some uncertainty continues to surround both the quantity and quality of the radiation released by these two nuclear devices, particularly the Hiroshima bomb. A recent reassessment suggests that the gamma radiation estimates which have been used in the past may be too low at some distances and the neutron radiation estimates too high at all distances; moreover, the energies of the neutrons released now appear ``softer'' than previously conjectured. These uncertainties not sufficiently large, however, to compromise the reality of the increased frequency of malignancy, but make estimates of the dose response, particularly in terms of gamma and neutron exposures, tentative.

The role of dust in mass loss from late-type stars

NASA Technical Reports Server (NTRS)

Jura, M.

1986-01-01

It is noted that, in almost all late-type stars with measured mass loss rates, there is sufficient momentum in the radiation to dominate the dynamics. The opacity of the material is sufficiently great to render radiation pressure important; the dust forms close enough to the central star for radiation pressure to account for the observed outflow velocities. Pulsations appear to be important in raising the material far enough above the photosphere for grains to condense.

LATE CONSEQUENCES WITH SMALL RONTGEN DOSES IN IRRADIATED CHILDREN (TENTATIVE REPORT) (in German)

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

Stasek, V.; Jakoubkova, J.; Brachfeld, K.

The authors searched for late reactions of radiation in children and young people, between the ages of 2 months and 5 years, who had been radiated on account of nontumorous diseases in the region of the throat. Ten to 15 years after the radiation 52 children and young people were examined. The examinations were carried out from the standpoint of radiotherapy, oto-rhino-laryngology, x- ray diagnostics, and pediatrics. In not quite half of those examimed local changes were stated and considered as late radiation damages: In 11 of those examined were disturbances of endocrinal coordination. Its appearance is, in the asmore » yet small compilation, relatively high. Considering that the first observation of this kind is being dealt with, and that there are not sufficient objective criteria, the authors keep for themselves a final evaluation only after verification on a greater number of radiated children and a control group. (auth)« less

The curative management of synchronous rectal and prostate cancer

PubMed Central

Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

2016-01-01

Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. Advances in knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients. PMID:26539631

Late effect of multiple daily fraction palliation schedule for advanced pelvic malignancies (RTOG 8502)

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

Spanos, W.J. Jr.; Clery, M.; Perez, C.A.

1994-07-30

The purpose was to determine late complication incidence for pelvic palliation using accelerated multiple daily fraction radiation [Radiation Therapy Oncology Group (RTOG) 8502]. None of the patients with < 30 Gy (less than three courses) developed late toxicity. A total of 11/193 (6%) developed Grade 3+ late toxicity (nine Grade 3, on Grade 4, one Grade 5). Actuarial analysis of complication rate by survival time for Grades 3, 4, and 5 shows a cumulative incidence for complications after 6 months that plateaus at 6.9% by 18 months. The cumulative incidence for Grades 4 and 5 is 2.0% by 12 months.more » The difference in late effect for the 2-week rest vs. 4-week rest was not statistically different (p = .47). Patient factors evaluated for increased risk of late complications included prior surgeries, age, sex, KPS and primary. None were found to have significant statistical correlations with late effects. The crude late complications rate is 6%. Actuarial analysis using cumulative incidence shows 6.9% by 18 months. This represents a significant decrease in late complications from 49% seen with higher dose per fraction (10 Gy {times} 3) piloted by Radiation Therapy Oncology Group (7905) for a similar group of patients. Long-term analysis of late complication indicates this schedule can be used in the pelvis with relatively low incidence of complication. This schedule has significant logistic benefits and has been shown to produce good tumor regression and excellent palliation of symptoms. 14 refs., 4 figs., 4 tabs.« less

Acute and Late Toxicity After Dose Escalation to 82 GyE Using Conformal Proton Radiation for Localized Prostate Cancer: Initial Report of American College of Radiology Phase II Study 03-12

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

Coen, John J., E-mail: jcoen@partners.org; Bae, Kyounghwa; Zietman, Anthony L.

Purpose: Several randomized trials have shown a benefit of dose escalation to 78 to 79 Gy for men treated with external radiation for localized prostate cancer. Single-institution data suggest a benefit with even higher doses. American College of Radiology 03-12 is a Phase II trial testing the safety and efficacy of 82 GyE (Gray equivalent) delivered with conformal proton radiation. Methods and Materials: From 2003-2006, 85 men with localized prostate cancer were accrued to American College of Radiology 03-12. Eighty-four were eligible for analysis. They were treated with conformal proton radiation alone to a total dose of 82 GyE. Themore » study was designed to test whether the rate of 18-month Grade 3+ late toxicity was greater than 10%. Results: The median follow-up was 31.6 months. Regarding treatment-related acute toxicity, there were 39 Grade 1 cases (46%), 19 Grade 2 cases (23%) and 2 Grade 3 cases (2%). Regarding genitourinary/gastrointestinal toxicity, there were 42 Grade 1 cases (50%), 12 Grade 2 cases (14%) and 1 Grade 3 case (1%). Regarding late toxicity, there were 28 Grade 1 cases (33%), 22 Grade 2 cases (26%), 6 Grade 3 cases (7%), and 1 Grade 4 case (1%). The late genitourinary/gastrointestinal rates were the same. The estimated rate of Grade 3+ late toxicity at 18 months was 6.08%. Conclusions: Although not free of late toxicity, 82 GyE at 2 GyE per fraction delivered with conformal proton radiation did not exceed the late morbidity target tested in this trial. There was sufficient morbidity, however, that this may be the maximal dose that can be delivered safely with this technique and fractionation.« less

Sexually transmitted diseases of the anus and rectum: Causal agents, coinfections, HIV infection and high-risk sexual behaviour.

PubMed

Morgado-Carrasco, Daniel; Alsina Gibert, Mercè; Bosch Mestres, Jordi; Álvarez Martínez, Miriam; Blanco Arévalo, José Luís; Fuertes de Vega, Irene

2018-04-18

Sexually transmitted infections of the rectum and anus (STI-RA) mainly affect men who have sex with men (MSM). The incidence of STI-RA among them has increased in recent years. Retrospective study in patients with diagnoses of STI-RA in an STI unit during the years 2014 and 2015. Epidemiological, clinical and microbiological data were collected. We included 95 patients, all of whom were MSM; 88.42% were HIV+; 67.17% did not use a condom during their most recent sexual intercourse; 17.91% had had sex with sex workers and 72.22% had used drugs during sexual intercourse during the previous year. A percentage of 32.92 reported symptoms that had lasted longer than 30 days. Lymphogranuloma venereum (LGV) was diagnosed in 54.73% of the patients. All patients who presented with proctitis and perianal ulcers were diagnosed with LGV infection. All those who presented perianal ulcers without proctitis were diagnosed with syphilis. All the patients affected by STI-RA were MSM, most of them HIV+, had engaged in high-risk sexual behaviour and had suffered prolonged symptomatology. Clinical and microbiological characteristics of STI-AR could help adjust the empiric therapy. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Minimally Invasive Radiation Biodosimetry and Evaluation of Organ Responses

DTIC Science & Technology

2016-10-01

radiation exposure, potentially leading to Acute Radiation Syndromes (ARS) and Delayed Effects of Acute ...underlying conditions and inherent variations. 2. KEYWORDS Radiation Biodosimetry, Radiation Biomarkers, microRNA, Acute Radiation Syndromes ... syndromes and delayed effects of acute radiation exposure. We expect to identify the circulating miRNA biomarkers as early predictors of late effects

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

Morota, Madoka; Gomi, Kotaro; Kozuka, Takuyo

Purpose: To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas. Methods and Materials: From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoringmore » scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer. Results: The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005). Conclusion: The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.« less

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

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

Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men receivedmore » CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen.« less

Late cataractogenesis caused by particulate radiations and photons in long-lived mammalian species

NASA Technical Reports Server (NTRS)

Lett, J. T.; Lee, A. C.; Cox, A. B.; Wood, D. H.

1989-01-01

Radiation cataractogenesis induced by small acute doses of particulate radiations and photons in the New Zealand white rabbit (Oryctolagus cuniculus), the beagle dog (Canis familiaris) and the rhesus monkey (Macaca mulatta) is discussed in the context of the use of animal models to assess the radiation hazards faced by humans during lengthy sojourns in deep space. Attention is paid to (1) the importance of lifespan studies with long-lived species - the above animals have median lifespans in captivity of 5-7, 13-14 and 25 years, respectively; and (2) the magnitudes of possible dose thresholds for cataractogenesis from sparsely ionizing radiations and the modifications of those thresholds by the late degenerative phase of the phenomenon.

A new basal hadrosauroid dinosaur from the Late Cretaceous of Uzbekistan and the early radiation of duck-billed dinosaurs.

PubMed

Sues, Hans-Dieter; Averianov, Alexander

2009-07-22

Levnesovia transoxiana gen. et sp. nov., from the Late Cretaceous (Middle-Late Turonian) of Uzbekistan, is the oldest well-documented taxon referable to Hadrosauroidea sensu Godefroit et al. It differs from a somewhat younger and closely related Bactrosaurus from Inner Mongolia (China) by a tall sagittal crest on the parietals and the absence of club-shaped dorsal neural spines in adult specimens. Levnesovia, Bactrosaurus and possibly Gilmoreosaurus represent the earliest radiation of Hadrosauroidea, which took place during the Cenomanian-Turonian and possibly in North America. The second, Santonian-age radiation of Hadrosauroidea included Aralosaurus, Hadrosauridae and lineages leading to Tanius (Campanian) and Telmatosaurus (Maastrichtian). Hadrosauridae appears to be monophyletic, but Hadrosaurinae and Lambeosaurinae originated in North America and Asia, respectively.

Mergers of Non-spinning Black-hole Binaries: Gravitational Radiation Characteristics

NASA Technical Reports Server (NTRS)

Baker, John G.; Boggs, William D.; Centrella, Joan; Kelly, Bernard J.; McWilliams, Sean T.; vanMeter, James R.

2008-01-01

We present a detailed descriptive analysis of the gravitational radiation from black-hole binary mergers of non-spinning black holes, based on numerical simulations of systems varying from equal-mass to a 6:1 mass ratio. Our primary goal is to present relatively complete information about the waveforms, including all the leading multipolar components, to interested researchers. In our analysis, we pursue the simplest physical description of the dominant features in the radiation, providing an interpretation of the waveforms in terms of an implicit rotating source. This interpretation applies uniformly to the full wavetrain, from inspiral through ringdown. We emphasize strong relationships among the l = m modes that persist through the full wavetrain. Exploring the structure of the waveforms in more detail, we conduct detailed analytic fitting of the late-time frequency evolution, identifying a key quantitative feature shared by the l = m modes among all mass-ratios. We identify relationships, with a simple interpretation in terms of the implicit rotating source, among the evolution of frequency and amplitude, which hold for the late-time radiation. These detailed relationships provide sufficient information about the late-time radiation to yield a predictive model for the late-time waveforms, an alternative to the common practice of modeling by a sum of quasinormal mode overtones. We demonstrate an application of this in a new effective-one-body-based analytic waveform model.

Mergers of nonspinning black-hole binaries: Gravitational radiation characteristics

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

Baker, John G.; Centrella, Joan; Kelly, Bernard J.

2008-08-15

We present a detailed descriptive analysis of the gravitational radiation from black-hole binary mergers of nonspinning black holes, based on numerical simulations of systems varying from equal mass to a 6 ratio 1 mass ratio. Our primary goal is to present relatively complete information about the waveforms, including all the leading multipolar components, to interested researchers. In our analysis, we pursue the simplest physical description of the dominant features in the radiation, providing an interpretation of the waveforms in terms of an implicit rotating source. This interpretation applies uniformly to the full wave train, from inspiral through ringdown. We emphasizemore » strong relationships among the l=m modes that persist through the full wave train. Exploring the structure of the waveforms in more detail, we conduct detailed analytic fitting of the late-time frequency evolution, identifying a key quantitative feature shared by the l=m modes among all mass ratios. We identify relationships, with a simple interpretation in terms of the implicit rotating source, among the evolution of frequency and amplitude, which hold for the late-time radiation. These detailed relationships provide sufficient information about the late-time radiation to yield a predictive model for the late-time waveforms, an alternative to the common practice of modeling by a sum of quasinormal mode overtones. We demonstrate an application of this in a new effective-one-body-based analytic waveform model.« less

2014 UK national guideline for the management of anogenital herpes.

PubMed

Patel, Raj; Green, John; Clarke, Emily; Seneviratne, Kanchana; Abbt, Naomi; Evans, Ceri; Bickford, Jane; Nicholson, Marian; O'Farrell, Nigel; Barton, Simon; FitzGerald, Mark; Foley, Elizabeth

2015-10-01

These guidelines concern the management of anogenital herpes simplex virus infections in adults and give advice on diagnosis, management, and counselling of patients. This guideline replaces the 2007 BASHH herpes guidelines and includes new sections on herpes proctitis, key points to cover with patients regarding transmission and removal of advice on the management of HSV in pregnancy which now has a separate joint BASHH/RCOG guideline. © The Author(s) 2015.

Cavernosal Abscess due to Streptococcus Anginosus: A Case Report and Comprehensive Review of the Literature

PubMed Central

Dugdale, Caitlin M.; Tompkins, Andrew J.; Reece, Rebecca M.; Gardner, Adrian F.

2013-01-01

Corpus cavernosum abscesses are uncommon with only 23 prior reports in the literature. Several precipitating factors for cavernosal infections have been described including injection therapy for erectile dysfunction, trauma, and priapism. Common causal organisms include Staphylococcus aureus, Streptococci, and Bacteroides. We report a unique case of a corpus cavernosum abscess due to proctitis with hematological seeding and review the literature on cavernosal abscesses. PMID:24917758

Radiation therapy in the neonate

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

Littman, P.; D'Angio, G.J.

Radiation therapy (RT) is frequently used in the management of children with cancer, but neonatal neoplasms are rare. Newborns represent 1.5% of the children with malignant diseases in the Tumor Registry at the Children's Hospital of Philadelphia over the last 30 years. Thus, occasionally the pediatrics radiation therapist must consider treating the very young infant. The specific radiation effects on growth and development must be weighed in reaching a therapeutic decision. All children are vulnerable to the late effects of radiation therapy, but the neonates may be more susceptible because of the immaturity of important organs such as the brain,more » lung, liver, kidney, and bone. In general, radiation therapy, should be avoided during the first several weeks of life because of the potential increased sensitivity of the liver and kidneys during that period. If radiation therapy is used at all during infancy, the benefits must be weighed against the possibility of significant late effects. Increasing knowledge of pediatric neoplasms has shown that some tumors (such as mesoblastic nephroma) require no treatment except for surgical excision; and other tumors, such as Stage IV-S neuroblastoma, may require very little treatment. In those tumors that require radiation therapy, the use of chemotherapy may allow reduction of the radiation dose. Furthermore, alterations of time-dose-fractionation schemes and careful attention to tumor volume with the use of special techniques, such as ''shrinking fields,'' may decrease the late adverse effects of treatment.« less

Late temporal lobe necrosis after conventional radiotherapy for carcinoma of maxillary sinus.

PubMed

Kanakamedala, Madhava R; Mahta, Ali; Liu, Jianlin; Kesari, Santosh

2012-12-01

Cerebral radiation necrosis is a serious late complication after conventional radiotherapy that can present with focal neurologic deficits or with more generalized signs and symptoms of increased intracranial pressure, depending on the location. The incidence and severity of radionecrosis are dose-volume dependent. We report a case of cerebral radiation necrosis 5 years after radiotherapy for a maxillary sinus carcinoma.

Diagnostic accuracy of ultrasonic histogram features to evaluate radiation toxicity of the parotid glands: a clinical study of xerostomia following head-and-neck cancer radiotherapy.

PubMed

Yang, Xiaofeng; Tridandapani, Srini; Beitler, Jonathan J; Yu, David S; Chen, Zhengjia; Kim, Sungjin; Bruner, Deborah W; Curran, Walter J; Liu, Tian

2014-10-01

To investigate the diagnostic accuracy of ultrasound histogram features in the quantitative assessment of radiation-induced parotid gland injury and to identify potential imaging biomarkers for radiation-induced xerostomia (dry mouth)-the most common and debilitating side effect after head-and-neck radiotherapy (RT). Thirty-four patients, who have developed xerostomia after RT for head-and-neck cancer, were enrolled. Radiation-induced xerostomia was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity scale. Ultrasound scans were performed on each patient's parotids bilaterally. The 34 patients were stratified into the acute-toxicity groups (16 patients, ≤ 3 months after treatment) and the late-toxicity group (18 patients, > 3 months after treatment). A separate control group of 13 healthy volunteers underwent similar ultrasound scans of their parotid glands. Six sonographic features were derived from the echo-intensity histograms to assess acute and late toxicity of the parotid glands. The quantitative assessments were compared to a radiologist's clinical evaluations. The diagnostic accuracy of these ultrasonic histogram features was evaluated with the receiver operating characteristic (ROC) curve. With an area under the ROC curve greater than 0.90, several histogram features demonstrated excellent diagnostic accuracy for evaluation of acute and late toxicity of parotid glands. Significant differences (P < .05) in all six sonographic features were demonstrated between the control, acute-toxicity, and late-toxicity groups. However, subjective radiologic evaluation cannot distinguish between acute and late toxicity of parotid glands. We demonstrated that ultrasound histogram features could be used to measure acute and late toxicity of the parotid glands after head-and-neck cancer RT, which may be developed into a low-cost imaging method for xerostomia monitoring and assessment. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Potential pre-cataractous markers induced by low-dose radiation effects in cultured human lens cells

NASA Astrophysics Data System (ADS)

Blakely, E.; McNamara, M.; Bjornstad, K.; Chang, P.

The human lens is one of the most radiosensitive organs of the body. Cataract, the opacification of the lens, is a late-appearing response to radiation damage. Recent evidence indicates that exposure to relatively low doses of space radiation are associated with an increased incidence and early appearance of human cataracts (Cucinotta et al., Radiat. Res. 156:460-466, 2001). Basic research in this area is needed to integrate the early responses of various late-responding tissues into our understanding and estimation of radiation risk for space travel. In addition, these studies may contribute to the development of countermeasures for the early lenticular changes, in order to prevent the late sequelae. Radiation damage to the lens is not life threatening but, if severe, can affect vision unless surgically corrected with synthetic lens replacement. The lens, however, may be a sensitive detector of radiation effects for other cells of ectodermal origin in the body for which there are not currently clear endpoints of low-dose radiation effects. We have investigated the dose-dependent expression of several radiation-responsive endpoints using our in vitro model of differentiating human lens epithelial cells (Blakely et al., Investigative Ophthalmology &Visual Sciences, 41(12):3898-3907, 2000). We have investigated radiation effects on several gene families that include, or relate to, DNA damage, cytokines, cell-cycle regulators, cell adhesion molecules, cell cytoskeletal function and apoptotic cell death. In this paper we will summarize some of our dose-dependent data from several radiation types, and describe the model of molecular and cellular events that we believe may be associated with precataractous events in the human lens after radiation exposure. This work was supported by NASA Grant #T-965W.

Gravitational Radiation Characteristics of Nonspinning Black-Hole Binaries

NASA Technical Reports Server (NTRS)

Kelly, B. J.; Baker, J. G.; Boggs, W. D.; Centrella, J. M.; vanMeter, J. R.; McWilliams, S. T.

2008-01-01

We present a detailed descriptive analysis of the gravitational radiation from binary mergers of non-spinning black holes, based on numerical relativity simulations of systems varying from equal-mass to a 6:1 mass ratio. Our analysis covers amplitude and phase characteristics of the radiation, suggesting a unified picture of the waveforms' dominant features in terms of an implicit rotating source, applying uniformly to the full wavetrain, from inspiral through ringdown. We construct a model of the late-stage frequency evolution that fits the l = m modes, and identify late-time relationships between waveform frequency and amplitude. These relationships allow us to construct a predictive model for the late-time waveforms, an alternative to the common practice of modelling by a sum of quasinormal mode overtones. We demonstrate an application of this in a new effective-one-body-based analytic waveform model.

XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

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

Seibold, Petra; Behrens, Sabine; Schmezer, Peter

Purpose: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress–related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy. Methods and Materials: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Totalmore » Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence. Results: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (−0.08, 95% confidence interval −0.15 to −0.02, P=.016). Conclusions: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients.« less

Lifecycle of laser-produced air sparks

DOE PAGES

Harilal, S. S.; Brumfield, B. E.; Phillips, M. C.

2015-06-03

Here, we investigated the lifecycle of laser-generated air sparks or plasmas using multiple plasma diagnostic tools. The sparks were generated by focusing the fundamental radiation from an Nd:YAG laser in air, and studies included early and late time spark dynamics, decoupling of the shock wave from the plasma core, emission from the spark kernel, cold gas excitation by UV radiation, shock waves produced by the air spark, and the spark's final decay and turbulence formation. The shadowgraphic and self-emission images showed similar spark morphology at earlier and late times of its lifecycle; however, significant differences are seen in the midlifemore » images. Spectroscopic studies in the visible region showed intense blackbody-type radiation at early times followed by clearly resolved ionic, atomic, and molecular emission. The detected spectrum at late times clearly contained emission from both CN and N 2 +. Additional spectral features have been identified at late times due to emission from O and N atoms, indicating some degree of molecular dissociation and excitation. Detailed spatially and temporally resolved emission analysis provides insight about various physical mechanisms leading to molecular and atomic emission by air sparks, including spark plasma excitation, heating of cold air by UV radiation emitted by the spark, and shock-heating.« less

Lifecycle of laser-produced air sparks

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

Harilal, S. S., E-mail: hari@pnnl.gov; Brumfield, B. E.; Phillips, M. C.

2015-06-15

We investigated the lifecycle of laser-generated air sparks or plasmas using multiple plasma diagnostic tools. The sparks were generated by focusing the fundamental radiation from an Nd:YAG laser in air, and studies included early and late time spark dynamics, decoupling of the shock wave from the plasma core, emission from the spark kernel, cold gas excitation by UV radiation, shock waves produced by the air spark, and the spark's final decay and turbulence formation. The shadowgraphic and self-emission images showed similar spark morphology at earlier and late times of its lifecycle; however, significant differences are seen in the midlife images.more » Spectroscopic studies in the visible region showed intense blackbody-type radiation at early times followed by clearly resolved ionic, atomic, and molecular emission. The detected spectrum at late times clearly contained emission from both CN and N{sub 2}{sup +}. Additional spectral features have been identified at late times due to emission from O and N atoms, indicating some degree of molecular dissociation and excitation. Detailed spatially and temporally resolved emission analysis provides insight about various physical mechanisms leading to molecular and atomic emission by air sparks, including spark plasma excitation, heating of cold air by UV radiation emitted by the spark, and shock-heating.« less

PET evaluation of late cerebral effect in advanced radiation therapy techniques for cranial base tumors.

PubMed

Alongi, Pierpaolo; Iaccarino, Leonardo; Losa, Marco; Del Vecchio, Antonella; Gerevini, Simonetta; Plebani, Valentina; Di Muzio, Nadia; Mortini, Pietro; Gianolli, Luigi; Perani, Daniela

2018-05-25

Even though the benefits of radiation therapy are well established, it is important to recognize the broad spectrum of radiation-induced changes, particularly in the central nervous system. The possible damage to the brain parenchyma may have clinical consequences and in particular cognitive impairment might be one of the major complication of radiotherapy. To date, no studies have investigated the effects of focal radiation therapy on brain structure and function together with the assessment of their clinical outcomes at a long follow-up. In this prospective study, we evaluated in six patients the possible brain late effects after radiation therapy, using a standardized neuropsychological battery, MRI and 18F-FDG PET using SPM and semi-quantitative methods, in patients affected by cranial base tumors who underwent gamma knife or tomotherapy. Neuropsychological examinations showed no cognitive impairment after the treatment. In all patients, both MRI assessment and 18F-FDG-PET did not reveal any local or distant anatomical and metabolic late effects. The present study support the safety of advanced radiation therapy techniques. 18F-FDG-PET, using SPM and semi-quantitative methods, might be a valuable tool to evaluate the cerebral radiotoxicity in patients treated for brain neoplasms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

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

Krema, Hatem, E-mail: htmkrm19@yahoo.com; Heydarian, Mostafa; Beiki-Ardakani, Akbar

2013-07-01

Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log–rank test compared the estimates. Results: The median follow-up was 46more » months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.« less

Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation.

PubMed

Beltrán-Pardo, Eliana; Jönsson, K Ingemar; Harms-Ringdahl, Mats; Haghdoost, Siamak; Wojcik, Andrzej

2015-01-01

Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at ~ 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation.

Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation

PubMed Central

Beltrán-Pardo, Eliana; Jönsson, K. Ingemar; Harms-Ringdahl, Mats; Haghdoost, Siamak; Wojcik, Andrzej

2015-01-01

Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at ~ 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation. PMID:26208275

[Lymphogranuloma venereum].

PubMed

Vyšatová, Michaela

2017-01-01

Lymphogranuloma venereum belongs to the sexually transmitted diseases. The disease is caused by Chlamydia trachomatis serotypes L1, L2 and L3. In the beginning of the 21st century there has been observed a large increase in the incidence of this disease in the world. There is a frequent co-occurrence with other sexually transmitted diseases (HIV, syphilis, gonorrhea, hepatitis C). Predominantly this disease affects homosexuals, in which case the first manifestation of the disease may be proctitis or proctocolitis.

Did L Strains Responsible for Lymphogranuloma Venereum Proctitis Spread Among People With Genital Chlamydia trachomatis Infection in France in 2013?

PubMed

Touati, Arabella; Vernay-Vaisse, Chantal; Janier, Michel; Le Hen, Isabelle; Charlois, Cécile; Dhotte, Philippe; Decré, Dominique; Bébéar, Cécile; de Barbeyrac, Bertille

2016-06-01

We retrospectively analyzed 1802 nonrectal Chlamydia trachomatis-positive specimens to determine if the L strains responsible for rectal Lymphogranuloma venereum in men who have sex with men could spread to the heterosexual population. No evidence for Lymphogranuloma venereum transmission among heterosexuals in France was observed in 2013. L2b strains seem to be restricted to the men who have sex with men population.

Sexually Transmitted Infections: Experience in a Multidisciplinary Clinic in a Tertiary Hospital (2010-2013).

PubMed

Moreno-Ribera, N; Fuertes-de Vega, I; Blanco-Arévalo, J L; Bosch-Mestres, J; González-Cordón, A; Estrach-Panella, T; García-de Olalla, P; Alsina-Gibert, M

2016-04-01

The number of consultations for sexually transmitted infections (STIs) is increasing in Spain. The aim of this study was to describe and analyze the epidemiological, behavioral, clinical, and microbiological characteristics of patients registered at the STI unit of a tertiary hospital. This was a retrospective, single-center descriptive study carried out between 2010 and 2013 in a multidisciplinary unit specialized in STIs, situated in a tertiary hospital. Epidemiological, clinical, and behavioral data were gathered using a face-to-face interview and a standardized questionnaire. Samples were collected for microbiology analysis. The study included 546 patients: 96% were men, 41% had human immunodeficiency virus (HIV) infection, and 56% were men who have sex with men. The reasons for consultation were the following: urethritis; genital, anal, or perianal ulcers; proctitis; oral ulcers; sexual contact with a person with a known STI; and high-risk sexual contact. The most common microbiological diagnoses were Neisseria gonorrhoeae in urethritis, Treponema pallidum in genital and anal or perianal ulcers, and Chlamydia trachomatis lymphogranuloma venereum serovars in proctitis. The highest prevalences of the main STIs studied occurred in homosexual men with HIV infection. This study confirms the increase in the incidence of STIs in recent years and the epidemiological characteristics of the HIV/STI epidemic in Spain. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications.

PubMed

Richter, James M; Arshi, Nabeela K; Oster, Gerry

2016-01-01

Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate ("5-ASA"), mesalamine suppository, or mesalamine enema ("UP Rx"). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations.

Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications

PubMed Central

Richter, James M.; Arshi, Nabeela K.; Oster, Gerry

2016-01-01

Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate (“5-ASA”), mesalamine suppository, or mesalamine enema (“UP Rx”). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations. PMID:27446860

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

Machtay, Mitchell, E-mail: mitchell.machtay@uhhospitals.org; Moughan, Jennifer; Farach, Andrew

Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis asmore » chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is common in long-term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.« less

The CAROLE (CArdiac Related Oncologic Late Effects) Study

ClinicalTrials.gov

2018-03-29

Coronary Artery Disease; Cardiac Disease; Cardiac Toxicity; Radiation; Radiation Therapy; Atherosclerotic Heart Disease; Cardiotoxicity; Breast Cancer; Lung Cancer; Lymphoma; Cancer; Carcinoma, Intraductal, Noninfiltrating

[Application of the life table method to the estimation of late complications of normal tissues after radiotherapy].

PubMed

Morita, K; Uchiyama, Y; Tominaga, S

1987-06-01

In order to evaluate the treatment results of radiotherapy it is important to estimate the degree of complications of the surrounding normal tissues as well as the frequency of tumor control. In this report, the cumulative incidence rate of the late radiation injuries of the normal tissues was calculated using the modified actuarial method (Cutler-Ederer's method) or Kaplan-Meier's method, which is usually applied to the calculation of the survival rate. By the use of this method of calculation, an accurate cumulative incidence rate over time can be easily obtained and applied to the statistical evaluation of the late radiation injuries.

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

Ampuero, F.; Doss, L.L.; Khan, M.

Twenty-eight patients with locally advanced malignancies of the cervix and vagina were treated with a combination of external radiation therapy and after loading Syed-Neblett iridium template. There were 22 patients with squamous cell cancer and two patients with adenocarcinomas of the cervix. Four patients with squamous cell cancer of the vagina were treated with this method. Only patients with locally advanced disease (cervical lesion >4 cm in diameter) and poor vagnal anatomy were selected for this modality of therapy. In this series the incidence of distant failures of 39% seems to confirm the significance of local volume of disease asmore » a prognostic indicator; despite a local control rate of 59%, only 33% of the patients are alive from 25-51 months. Complications occurred in 12 patients (42%). Six patients (22%) developed severe rectal stricture or rectovaginal fistula necessitating diverting sigmoid colostomy; five patients (18%) developed hemorrhagic proctitis with diarrhea and tenesmus; one patient developed vaginal vault necrosis. Complications occurred 7 to 24 months following therapy. Six of the 12 patients developing complications are dead of disease. On the basis of this study and because of the low cure rate and high incidence of complications, the value of the Syed-Neblett template in locally advanced gynecologic malignancies should be reconsidered.« less

Spatial features of dose-surface maps from deformably-registered plans correlate with late gastrointestinal complications

NASA Astrophysics Data System (ADS)

Moulton, Calyn R.; House, Michael J.; Lye, Victoria; Tang, Colin I.; Krawiec, Michele; Joseph, David J.; Denham, James W.; Ebert, Martin A.

2017-05-01

This study investigates the associations between spatial distribution of dose to the rectal surface and observed gastrointestinal toxicities after deformably registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate brachytherapy (HDRBT) prostate cancer treatment. The study contains data for 118 patients where the HDRBT CT was deformably-registered to the EBRT CT. The EBRT and registered HDRBT TG43 dose distributions in a reference 2 Gy/fraction were 3D-summed. Rectum dose-surface maps (DSMs) were obtained by virtually unfolding the rectum surface slice-by-slice. Associations with late peak gastrointestinal toxicities were investigated using voxel-wise DSM analysis as well as parameterised spatial patterns. The latter were obtained by thresholding DSMs from 1-80 Gy (increment  =  1) and extracting inferior-superior extent, left-right extent, area, perimeter, compactness, circularity and ellipse fit parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate features with toxicities. Rectal bleeding, stool frequency, diarrhoea and urgency/tenesmus were associated with greater lateral and/or longitudinal spread of the high doses near the anterior rectal surface. Rectal bleeding and stool frequency were also influenced by greater low-intermediate doses to the most inferior 20% of the rectum and greater low-intermediate-high doses to 40-80% of the rectum length respectively. Greater low-intermediate doses to the superior 20% and inferior 20% of the rectum length were associated with anorectal pain and urgency/tenesmus respectively. Diarrhoea, completeness of evacuation and proctitis were also related to greater low doses to the posterior side of the rectum. Spatial features for the intermediate-high dose regions such as area, perimeter, compactness, circularity, ellipse eccentricity and confinement to ellipse fits were strongly associated with toxicities other than anorectal pain. Consequently, toxicity is related to the shape of isodoses as well as dose coverage. The findings indicate spatial constraints on doses to certain sections of the rectum may be important for reducing toxicities and optimising dose.

Late recurrence of nonseminomatous germ cell tumor successfully treated with intensity-modulated radiation therapy.

PubMed

Kita, Yuki; Imamura, Masaaki; Mizowaki, Takashi; Norihisa, Yoshiki; Yoshimura, Koji; Hiraoka, Masahiro; Ogawa, Osamu

2013-08-01

We report the case of a 41-year-old man with a late recurrence of nonseminomatous germ cell tumor, which was successfully treated with intensity-modulated radiation therapy. For the residual retrocrural tumor invading the 11th and 12th thoracic vertebrae with an abnormal level of tumor marker (α-fetoprotein: 23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due to its neurotoxicity, and surgery could not be performed due to the location. In this situation, intensity-modulated radiation therapy achieved a complete response of tumor marker. The patient remained in complete clinical remission after 3 years. The efficacy of radiotherapy, especially intensity-modulated radiation therapy, for a nonseminomatous germ cell tumor is discussed.

Evaluation of Late Effects of Heavy-Ion Radiation on Mesenchymal Stem Cells

NASA Technical Reports Server (NTRS)

Gonda, S.R.; Behravesh, E.; Huff, J.L.; Johnson, F.

2005-01-01

The overall objective of this recently funded study is to utilize well-characterized model test systems to assess the impact of pluripotent stem cell differentiation on biological effects associated with high-energy charged particle radiation. These stem cells, specifically mesenchymal stem cells (MSCs), have the potential for differentiation into bone, cartilage, fat, tendons, and other tissue types. The characterization of the regulation mechanisms of MSC differentiation to the osteoblastic lineage by transcription factors, such as Runx2/Cbfa1 and Osterix, and osteoinductive proteins such as members of the bone morphogenic protein family are well established. More importantly, for late biological effects, MSCs have been shown to contribute to tissue restructuring and repair after tissue injury. The complex regulation of and interactions between inflammation and repair determine the eventual outcome of the responses to tissue injury, for which MSCs play a crucial role. Additionally, MSCs have been shown to respond to reactive oxygen species, a secondary effector of radiation, by differentiating. With this, we hypothesized that differentiation of MSCs can alter or exacerbate the damage initiated by radiation, which can ultimately lead to late biological effects of misrepair/fibrosis which may ultimately lead to carcinogenesis. Currently, studies are underway to examine high-energy X-ray radiation at low and high doses, approximately 20 and 200 Rad, respectively, on cytogenetic damage and gene modulation of isolated MSCs. These cells, positive for MSC surface markers, were obtained from three persons. In vitro cell samples were harvested during cellular proliferation and after both cellular recovery and differentiation. Future work will use established in vitro models of increasing complexity to examine the value of traditional 2D tissue-culture techniques, and utilize 3D in vitro tissue culture techniques that can better assess late effects associated with radiation.

Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

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

Huddart, Robert A., E-mail: robert.huddart@icr.ac.uk; Hall, Emma; Hussain, Syed A.

2013-10-01

Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. Themore » primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.« less

A Tocotrienol-Enriched Formulation Protects against Radiation-Induced Changes in Cardiac Mitochondria without Modifying Late Cardiac Function or Structure

PubMed Central

Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K.; Moros, Eduardo G.; Melnyk, Stepan B.; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

2015-01-01

Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling. PMID:25710576

A tocotrienol-enriched formulation protects against radiation-induced changes in cardiac mitochondria without modifying late cardiac function or structure.

PubMed

Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K; Moros, Eduardo G; Melnyk, Stepan B; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

2015-03-01

Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling.

Optical Coherence Tomography for Quantitative Assessment of Microstructural and Microvascular Alterations in Late Oral Radiation Toxicity

NASA Astrophysics Data System (ADS)

Davoudi, Bahar

More than half of head-and-neck cancer patients undergo radiotherapy at some point during their treatment. Even though the use of conformed therapeutic beams has increased radiation dose localization to the tumor, resulting in more normal tissue sparing, still, in many head-and-neck cancer patients, the healthy tissue of the oral cavity still receives a sizeable amount of radiation. This causes acute and / or late complications in these patients. The latter occur as late as several months or even years after the completion of treatment and are typically associated with severe symptoms. Currently, the clinical method for diagnosing these complications is visual examination of the oral tissue surface. However, it has been well established that such complications originate in subsurface oral tissue layers including its microvasculature. Therefore, to better understand the mechanism of these complications and to be able to diagnose them earlier, there exists a need for subsurface monitoring of the irradiated oral tissue. Histology has been used as such a tool for research purposes; however, its use in clinical diagnosis is limited due to its invasive and hazardous nature. Therefore, in this thesis, I propose to use optical coherence tomography (OCT) as a subsurface, micron-scale resolution optical imaging tool that can provide images of oral tissue subsurface layers down to a depth of 1-2 mm (structural OCT), as well as images demonstrating vessel morphology (speckle variance OCT) and blood flow information (Doppler OCT). This thesis explains the development of an OCT setup and an oral probe to acquire images in-vivo. Moreover, it introduces a software-based quantification platform for extracting specific biologically-meaningful metrics from the structural and vascular OCT images. It then describes the application of the developed imaging and quantification platform in a feasibility clinical study that was performed on 15 late oral radiation toxicity patients and 5 age-matched healthy volunteers. The results of this clinical study show that: 1) the value of the developed metrics (such as epithelium to lamina propria thickness, vessel diameter, and blood velocity) is significantly different between the two cohorts; 2) radiation-induced abnormalities in structural OCT images are primarily observed in the regions where the total radiation dose exceeded ˜50 Gy. The results of this study demonstrate the promising ability of the developed OCT imaging and quantification platform to highlight biologically meaningful differences between late oral radiation toxicity patients and healthy volunteers in the structural and vascular images. This methodology may also be used in prognostic studies to monitor the efficacy of the medication prescribed to late oral radiation toxicity patients.

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PubMed

Itakura, Katsumasa; Takahashi, Ikuno; Nakashima, Eiji; Yanagi, Masahide; Kawasaki, Ryo; Neriishi, Kazuo; Wang, Jie Jin; Wong, Tien Yin; Hida, Ayumi; Ohishi, Waka; Kiuchi, Yoshiaki

2015-08-01

To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

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

Lee, Larissa J.; Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu

2012-12-01

Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adversemore » Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the rectum.« less

Late effect of atomic bomb radiation on myeloid disorders: leukemia and myelodysplastic syndromes.

PubMed

Tsushima, Hideki; Iwanaga, Masako; Miyazaki, Yasushi

2012-03-01

Leukemia was the first malignancy linked to radiation exposure in atomic bomb survivors. Clear evidence of the dose-dependent excess risk of three major types of leukemia (acute lymphocytic leukemia, acute myeloid leukemia [AML], and chronic myeloid leukemia) was found, especially in people exposed at young ages. Such leukemia risks were at their highest in the late 1950s, and declined gradually thereafter over the past 50 years. Findings from recent risk analyses, however, suggest the persistence of AML risk even after 1990, and evidence of increased risk of myelodysplastic syndromes (MDS) due to atomic bomb radiation has recently been shown. High-risk MDS and forms involving complex chromosomal aberrations were found to be much more frequent in people exposed to higher radiation doses. These lines of epidemiological evidence suggest that the risk of radiation-induced hematological malignancies has persisted for six decades since the initial exposure.

Late radiation side-effects in three patients undergoing parotid irradiation for benign disease.

PubMed

Armour, A; Ghanna, P; O'Rielly, B; Habeshaw, T; Symonds, P

2000-01-01

We report three patients in whom standard radiation therapy was given and serious late radiation damage was seen. The first patient suffered recurrent parotiditis and a parotid fistula. He was treated initially with 20 Gy in ten fractions via a 300 kV field. Further irradiation was required 1 year later and 40 Gy was given in 2 Gy fractions by an oblique anterior and posterior wedged photon pair. Ten years later he developed localized temporal bone necrosis. The second patient, with pleomorphic salivary adenoma, developed localized temporal bone necrosis 6 years after 60 Gy had been given using standard fractionation and technique. The third patient received 55 Gy in 25 fractions for a pleomorphic salivary adenoma and after 3 years developed temporal bone necrosis. Sixteen years later the same patient developed cerebellar and brainstem necrosis. All patients developed chronic persistent infection during or shortly after the radiation therapy, which increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly.

Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.

PubMed

Wang, Dian; Zhang, Qiang; Eisenberg, Burton L; Kane, John M; Li, X Allen; Lucas, David; Petersen, Ivy A; DeLaney, Thomas F; Freeman, Carolyn R; Finkelstein, Steven E; Hitchcock, Ying J; Bedi, Manpreet; Singh, Anurag K; Dundas, George; Kirsch, David G

2015-07-10

We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS. © 2015 by American Society of Clinical Oncology.

Phase II Study of Vinorelbine and Estramustine in Combination With Conformational Radiotherapy for Patients With High-Risk Prostate Cancer

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

Carles, Joan, E-mail: jocarles@vhebron.ne; Nogue, Miguel; Sole, Josep M.

Purpose: To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer. Methods and Materials: Fifty patients received estramustine, 600 mg/m{sup 2} daily, and vinorelbine, 25 mg/m{sup 2}, on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years. Results: All patients were evaluated for response and toxicity. Progression-free survival at 5 yearsmore » was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patient's decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction. Conclusions: Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.« less

Lymphogranuloma venereum among patients presenting at the HIV/STI clinic in Antwerp, Belgium : a case series.

PubMed

Apers, Ludwig; Florence, Eric; Crucitti, Tania; Anwar, Nabila

2017-01-01

Objective of this study was to describe the patient characteristics and clinical presentation of laboratory confirmed lymphogranuloma venereum (LGV) cases, diagnosed at the Institute of Tropical Medicine (ITM), Antwerp, Belgium. Demographic and biomedical characteristics of all patients with chlamydia-positive sample results were retrieved for the years 2013 and 2014. Samples were obtained from both symptomatic and asymptomatic patients who consulted at the HIV/STI clinic. Fifty four patients with laboratory confirmed LGV were detected among 3885 nucleic acid amplification tests (NAATs) performed for the detection of chlamydia during the two years under review. Fifty three were men and equally fifty three had sex with men only (MSM). HIV (87%) and HCV (31.5%) were common concomitant infections, whilst anal gonorrhoea and syphilis were detected at the moment of the LGV diagnosis among 19 (35.2%) and 6 (11.0%) cases respectively. All cases were symptomatic, except one. The most frequent symptoms that were recorded could be categorised as proctitis (in 40 patients (74%)). Lymphadenopathy, anal and genital ulcers were signs that were present in 7 (13.0%), 4 (7.4%) and 2 patients (3.7%) respectively. LGV remains an important sexually transmitted disease among MSM. In this retrospective study, the far majority of LGV was detected amongst symptomatic persons. HCV, HIV, anal gonorrhoea and syphilis were associated co-infections. Proctitis in a high risk patient should alert the clinician for the possibility of an STI. © Acta Gastro-Enterologica Belgica.

Impact of rocket propulsion technology on the radiation risk in missions to Mars

NASA Astrophysics Data System (ADS)

Durante, M.; Bruno, C.

2010-10-01

Exposure to cosmic radiation is today acknowledged as a major obstacle to human missions to Mars. In fact, in addition to the poor knowledge on the late effects of heavy ions in the cosmic rays, simple countermeasures are apparently not available. Shielding is indeed very problematic in space, because of mass problems and the high-energy of the cosmic rays, and radio-protective drugs or dietary supplements are not effective. However, the simplest countermeasure for reducing radiation risk is to shorten the duration time, particularly the transit time to Mars, where the dose rate is higher than on the planet surface. Here we show that using nuclear electric propulsion (NEP) rockets, the transit time could be substantially reduced to a point where radiation risk could be considered acceptable even with the current uncertainty on late effects.

Clinical and dosimetric factors of radiation-induced esophageal injury: radiation-induced esophageal toxicity.

PubMed

Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

2005-05-07

To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus > or =60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). Concurrent chemotherapy and the maximal esophageal point dose > or =60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

Successful pregnancy after radiation therapy for carcinoma of the cervix

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

Whelton, James A.; McSweeney, Daniel J.

Radiosensitivity of the ovary is considered, and the possibility of recovery of ovarian function following pelvic radiotherapy is evaluated with reference to previously reported cases and a new case. In the standard radiation program of combined Ra and x-ray therapy currently employed for the control of carcinoma of the cervix, thc amount of radiation delivered to the gonads makes preservation of ovarian function nearly impossible. Even after Ra therapy alone for cervical cancer, continued ovarian activity as evidenced by regular menstruation is infrequent, and successful pregnancy after Ra treatment for a malignant growth on the cervix is an extremely raremore » occurrence. Data are tabulated for nine previous cases in which pregnancy occurred after radiotherapy for cervical carcinoma. In the present case, a 21-yr-old women was treated with 5000 mg-hr and became pregnant twice, four and six yrs later. No external x-ray therapy was given. The patient experienced vaginal bleeding consistent with a menstrual period in each of the first two months after Ra insertion but had total amenorrhea for the next year. Rectal bleeding and diarrhea six months later because of radiation proctitis. A cervical biopsy performed three yr later showed a severe radiation reaction. Regular menses commenced four months after this procedure. Both pregnancies terminated prematurely but in both instances an apparently normal infant was born, and no subsequent abnormalities in their growth, development, or behaviour were noted. In the reviewed group of cases, preservation of ovarian function was attributed in great measure to the increased distance of the ovaries from the Ra source because of an intrauterine gestation (five cases), recent parturition (one case), recent miscarriage (one case), and a large exophytic tumor (one case). The existence of an amenorrheic state for nine months in one earlier case and for 12 months in the present case indicates that the radiosensitive gonads were significantly affected by the action of radiation. The relative youth of these two patients may have played a role in the capacity of their ovaries to reestablish ovulation. The effect of radiation on the function of cervical dilatation in parturition was also discussed after a study of these cases. Because of radioinduced scarring of the cervix, cesarean section is usually necessary for delivery in such cases. Among the 10 children who were born of these mothers whose ovaries had received a subliminal castration dose of radiation there was no evidence of any gross congenital defect, but the follow-up on all of these children is incomplete and the possibility of a genetic defect in a future generation cannot be ruled out if children should be born to any of these individuals.« less

Late Effects Following Treatment of Hodgkin Lymphoma During Childhood and Adolescence. Results of the Hodgkin Lymphoma Late Effects Research Project.

PubMed

Dörffel, W; Riepenhausen, M; Lüders, H; Brämswig, J

2016-11-01

Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects have been observed. It was therefore an important aim of the cooperative pediatric HL therapy studies in Germany to reduce the number of late effects without jeopardizing the excellent treatment results. Progress and relapses of HL were analyzed to obtain important information for the future salvage therapy. All late effects were documented and their etiologies analyzed. Information obtained from bacterial infections and late deaths following splenectomy were used to inform patients at risk and their local physicians about necessary preventive measurements. Procarbazine was recognized as major gonadotoxic agent in boys and eliminated successively from the treatment regimens. Parenthood was normal in female patients when compared to the German female population documenting normal ovarian function except in patients with pelvic radiation. Radiation was the most important risk factor for thyroid diseases, cardiac late effects and subsequent malignant neoplasms, especially thyroid and breast cancer. A special screening program was initiated for women with chest radiotherapy, since they had a high risk of breast cancer already at a young age. The results of the HL Late Effects Research Project are important for the aftercare of patients and for the design of future HL treatment regimens. © Georg Thieme Verlag KG Stuttgart · New York.

Experience-Related Structural Changes of Degenerated Occipital White Matter in Late-Blind Humans – A Diffusion Tensor Imaging Study

PubMed Central

Dietrich, Susanne; Hertrich, Ingo; Kumar, Vinod; Ackermann, Hermann

2015-01-01

Late-blind humans can learn to understand speech at ultra-fast syllable rates (ca. 20 syllables/s), a capability associated with hemodynamic activation of the central-visual system. Thus, the observed functional cross-modal recruitment of occipital cortex might facilitate ultra-fast speech processing in these individuals. To further elucidate the structural prerequisites of this skill, diffusion tensor imaging (DTI) was conducted in late-blind subjects differing in their capability of understanding ultra-fast speech. Fractional anisotropy (FA) was determined as a quantitative measure of the directionality of water diffusion, indicating fiber tract characteristics that might be influenced by blindness as well as the acquired perceptual skills. Analysis of the diffusion images revealed reduced FA in late-blind individuals relative to sighted controls at the level of the optic radiations at either side and the right-hemisphere dorsal thalamus (pulvinar). Moreover, late-blind subjects showed significant positive correlations between FA and the capacity of ultra-fast speech comprehension within right-hemisphere optic radiation and thalamus. Thus, experience-related structural alterations occurred in late-blind individuals within visual pathways that, presumably, are linked to higher order frontal language areas. PMID:25830371

Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis.

PubMed

Choi, Yo Won; Munden, Reginald F; Erasmus, Jeremy J; Park, Kyung Joo; Chung, Woo Kyung; Jeon, Seok Chol; Park, Choong-Ki

2004-01-01

Radiation-induced lung disease (RILD) due to radiation therapy is common. Radiologic manifestations are usually confined to the lung tissue within the radiation port and are dependent on the interval after completion of treatment. In the acute phase, RILD typically manifests as ground-glass opacity or attenuation or as consolidation; in the late phase, it typically manifests as traction bronchiectasis, volume loss, and scarring. However, the use of oblique beam angles and the development of newer irradiation techniques such as three-dimensional conformal radiation therapy can result in an unusual distribution of these findings. Awareness of the atypical manifestations of RILD can be useful in preventing confusion with infection, recurrent malignancy, lymphangitic carcinomatosis, and radiation-induced tumors. In addition, knowledge of radiologic findings that are outside the expected pattern for RILD can be useful in diagnosis of infection or recurrent malignancy. Such findings include the late appearance or enlargement of a pleural effusion; development of consolidation, a mass, or cavitation; and occlusion of bronchi within an area of radiation-induced fibrosis. A comprehensive understanding of the full spectrum of these manifestations is important to facilitate diagnosis and management in cancer patients treated with radiation therapy. Copyright RSNA, 2004

Late esophageal toxicity after radiation therapy for head and neck cancer.

PubMed

Chen, Allen M; Li, Bao-Qing; Jennelle, Richard L S; Lau, Derick H; Yang, Claus C; Courquin, Jean; Vijayakumar, Srinivasan; Purdy, James A

2010-02-01

The aim of this study was to determine the incidence of esophageal toxicity after radiation therapy for head and neck cancer. The records of 211 patients treated by radiation therapy for head and neck cancer were reviewed to identify those with dysphagia lasting more than 90 days after therapy. Late toxicity criteria established by the Radiation Therapy Oncology Group were used to score the symptoms. The incidence of grade 3+ esophageal toxicity at 3 and 6 months was 30% and 19%, respectively. The rate of gastrotomy-tube dependence at 3 and 6 months was 20% and 11%, respectively. Hypopharyngeal and unknown primary site (p = .01, for both), T4 disease (p = .01), and the use of concurrent chemotherapy (p = .001) were associated with grade 3+ esophageal toxicity and stricture formation. A significant proportion of patients exhibit symptoms of esophageal toxicity after radiation therapy for head and neck cancer. Therefore, preventive strategies need further investigation. Copyright 2009 Wiley Periodicals, Inc.

[A Case of Rectal Syphilis Incidentally Found at Regular Medical Check-up].

PubMed

You, Ji Hong; Cho, Ki Won; Cha, Yoon Jin; Park, Hyo Jin

2016-10-25

Syphilis is a rare disease in the rectum. It is difficult to diagnose because the characteristics of the rectal syphilis rectal lesion are highly varied. The endoscopic findings of rectal syphilis are proctitis, ulcers, and masses. If rectal syphilis is suspected to be the cause for rectal lesions, it is important for physicians to consider the sexual history and sexual orientation of the patient. We report a case of incidental rectal syphilis in a 41-year-old man diagnosed during a regular medical check-up.

Lymphogranuloma Venereum-Serovar L2b Presenting With Painful Genital Ulceration: An Emerging Clinical Presentation?

PubMed

Haber, Roger; Maatouk, Ismaël; de Barbeyrac, Bertille; Bagot, Martine; Janier, Michel; Fouéré, Sébastien

2017-05-01

These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b presenting initially with edema and persistent painful ulceration illustrate that clinical manifestations of LGV in the current outbreak in men who have sex with men reflect the influence of both the serovars virulence and the host immune system and are not confined to proctitis. L2b serovar could have a particular high virulence profile, and the need for awareness of LGV as a cause of genital ulceration is crucial.

RBE for late somatic effects in mice irradiated with 60 MeV protons relative to X-rays.

NASA Technical Reports Server (NTRS)

Darden, E. B., Jr.; Clapp, N. K.; Bender, R. S.; Jernigan, M. C.; Upton, A. C.

1971-01-01

Investigation of the relative biological effectiveness of energetic protons for the induction of somatic effects in a mammal (mice) following whole body irradiation. The proton energy used approximates the mean energy for proton spectra accompanying solar events. The effects on longevity and the incidence of major neoplastic diseases are summarized. The results obtained suggest that medium energy proton irradiation is no more effective, and on the whole, probably less effective, than conventional X radiation for the induction of late radiation effects in the mouse.

Electromagnetic navigation-guided neuroendoscopic removal of radiation-induced intraforniceal cavernoma as a late complication of medulloblastoma treatment.

PubMed

Liby, Petr; Zamecnik, J; Kyncl, M; Zackova, J; Tichy, M

2017-11-01

Medulloblastoma is the most frequent malignant brain tumour in children. Radiation-induced cavernous haemangiomas (RICHs) are a known late complication of radiation exposure, especially in young children. We present a patient who underwent subtotal resection of posterior fossa medulloblastoma with subsequent chemotherapy and radiotherapy at the age of 10 years. A new lesion in the region of the left foramen of Monro appeared 16 years later. Based on the imaging results, metastasis or radiation-induced cavernoma was considered. The lesion had the same appearance on imaging as a rarely published intraventricular cavernoma of the foramen of Monro. Unlike the cavernoma of the foramen of Monro, this lesion was subependymal and intraforniceal. Using electromagnetic navigation and neuroendoscopy, the lesion was completely removed. Histopathological examination revealed a cavernous haemangioma. This is a unique case of intraforniceal paraforaminal cavernoma that was successfully removed endoscopically using electromagnetic neuronavigation and without neurological sequelae.

Radiation Therapy Did Not Induce Long-Term Changes in Rectal Mucosa: Results From the Randomized Scandinavian Prostate Cancer Group 7 Trial

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

Slagsvold, Jens Erik, E-mail: Jens.Erik.Slagsvold@stolav.no; Viset, Trond; Wibe, Arne

Purpose: To investigate long-term changes in the rectal mucosa after curative external beam radiation therapy in the treatment of prostate cancer. Methods and Materials: In the Scandinavian Prostate Cancer Group 7 trial, 880 men with locally advanced prostate cancer were randomized to hormonal therapy alone versus hormonal therapy plus radiation therapy to 70 Gy. A subcohort from this trial being randomized at our center (n=178) was invited to a study on late anorectal side effects during 2003-2005, approximately 5 years after treatment, including measuring health-reported quality of life and physician-assessed toxicity score by the Late Effects Normal Tissue Task Force/Subjective, Objective, Management, Analyticmore » (LENT/SOMA) and European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group score. Sixty-seven patients had a rectal mucosa biopsy. Sixty-four biopsies were included in the final analysis, of which 33 patients were randomized to hormonal treatment and 31 to hormonal treatment plus radiation therapy. The presence of fibrosis, number of capillaries, and lymphocyte infiltration was then evaluated by light microscopy. Results: The group receiving radiation therapy had significantly higher LENT/SOMA and function/bother scale scores than the group that only received hormonal treatment, but there was no significant difference in the presence of fibrosis, ectasia, number of capillaries in the lamina propria, or lymphocyte infiltration between the groups. Conclusion: Radiation therapy to 70 Gy to the prostate does not induce long-term microscopic mucosal changes in the rectum 5 years after treatment. This is in contrast to the general assumption that structural changes, including fibrosis, seen after radiation therapy include the mucosa. We speculate that the main late effects of radiation therapy on the structure of the rectum are located in the deeper layers of the rectal wall than the mucosa.« less

Space Radiation

NASA Technical Reports Server (NTRS)

Wu, Honglu

2006-01-01

Astronauts receive the highest occupational radiation exposure. Effective protections are needed to ensure the safety of astronauts on long duration space missions. Increased cancer morbidity or mortality risk in astronauts may be caused by occupational radiation exposure. Acute and late radiation damage to the central nervous system (CNS) may lead to changes in motor function and behavior, or neurological disorders. Radiation exposure may result in degenerative tissue diseases (non-cancer or non-CNS) such as cardiac, circulatory, or digestive diseases, as well as cataracts. Acute radiation syndromes may occur due to occupational radiation exposure.

Impact on the Japanese atomic bomb survivors of radiation received from the bombs.

PubMed

Cullings, Harry M

2014-02-01

The Radiation Effects Research Foundation (RERF) studies various cohorts of Japanese atomic bomb survivors, the largest being the Life Span Study (LSS), which includes 93,741 persons who were in Hiroshima or Nagasaki at the times of the bombings; there are also cohorts of persons who were exposed in utero and survivors' children. This presentation attempts to summarize the total impact of the radiation from the bombs on the survivors from both an individual perspective (both age-specific and integrated lifetime risk, along with a measure of life expectancy that describes how the risk affects the individual given age at exposure) and a group perspective (estimated numbers of excess occurrences in the cohort), including both early and late effects. As survivors' doses ranged well into the acutely lethal range at closer distances, some of them experienced acute signs and symptoms of radiation exposure in addition to being at risk of late effects. Although cancer has always been a primary concern among late effects, estimated numbers of excess cancers and hematopoietic malignancies in the LSS are a small fraction of the total due to the highly skewed dose distribution, with most survivors receiving small doses. For example, in the latest report on cancer incidence, 853 of 17,448 incident solid cancers were estimated to be attributable to radiation from the bombs. RERF research indicates that risk of radiation-associated cancer varies among sites and that some benign tumors such as uterine myoma are also associated with radiation. Noncancer late effects appear to be in excess in proportion to radiation dose but with an excess relative risk about one-third that of solid cancer and a correspondingly small overall fraction of cases attributable to radiation. Specific risks were found for some subcategories, particularly circulatory disease, including stroke and precedent conditions such as hypertension. Radiation-related cataract in the atomic bomb survivors is well known, with evidence in recent years of risk at lower dose levels than previously appreciated. In addition to somatic effects, survivors experienced psychosocial effects such as uncertainty, social stigma, or rejection, and other social pressures. Developmental deficits associated with in utero exposure, notably cognitive impairment, have also been described. Interaction of radiation with other risk factors has been demonstrated in relation to both cancer and noncancer diseases. Current research interests include whether radiation increases risk of diabetes or conditions of the eye apart from cataract, and there continues to be keen interest as to whether there are heritable effects in survivors' children, despite negative findings to date. Introduction of Impact on the Japanese Atomic- Bomb Survivors (Video 1:52, http://links.lww.com/HP/A29).

[Local application of dimethyl sulfoxide at different concentrations to the prevention of radiation-induced damages in patient with cancer of the cervix uteri].

PubMed

Neklasova, N Iu; Sharinov, G M; Vinokurov, V L; Skrynditsa, G M

2006-01-01

to study the efficacy of dimethyl sulfoxide ((DMSO) at different concentrations in preventing radiation-induced rectal and urinary bladder damages in patients with cervix uteri cancer (CUC). combined radiation therapy (RT) was performed in 807 patients with CUC. In the control group (n = 221), RT was made, without applying radio-modified agents. An hour prior to a session of intracavitary irradiation, 10% DMSO solution was instilled into the rectum and urinary bladder in 113 patients and applications of metronidazole (MN) dissolved in 100% DSMO were made in 473 patients. Teleradiotherapy was performed, by using megavolt irradiation sources in the conventional fractionation mode; the total focal dose (TFD) was increased up to 40-46 Gy. Intracavitary irradiation was carried out on "AGAT-V" and "AGAT-VU" devices once weekly; the single focal dose in point A was 7 Gy; TFD was 49-56 Gy. 10% DMSO instillations reduced the incidence of late radiation-induced damages to the rectum and urinary bladder. In the control group, the incidence of these conditions was 19.0 and 9.5%, respectively; with the use of 10% DMSO, that was 8.8 and 7.1%. Applications of MN dissolved in 100% DMSO reduced the incidence of late radiation-induced damages to 1.7%. Local application of DMSO is a method for preventing late radiation-induced damages to the rectum and urinary bladder in patients with CUC. When the concentration of DMSO is increased, its preventive effect increases.

Late effects from particulate radiations in primate and rabbit tissues

NASA Astrophysics Data System (ADS)

Lett, J. T.; Cox, A. B.; Bergtold, D. S.; Lee, A. C.; Pickering, J. E.

Optic tissues in groups of New Zealand white rabbits were irradiated locally at different stages throughout the median life span of the species with a single dose (9 Gy) of 425 MeV/amu Ne ions (LET∞~30 keV/μm) and then inspected routinely for the progression of radiation cataracts. The level of early cataracts was found to be highest in the youngest group of animals irradiated (8 weeks old) but both the onset of late cataracts and loss of vision occurred earlier when animals were irradiated during the second half of the median life span. This age response can have serious implications in terms of space radiation hazards to man. Rhesus monkeys that had been subjected to whole-body skin irradiation (2.8 and 5.6 Gy) by 32 MeV protons (range in tissue ~ 1 cm) some twenty years previously were analysed for radiation damage by the propagation of skin fibroblasts in primary cultures. Such propagation from skin biopsies in MEM-α medium (serial cultivation) or in supplemented Ham's F-10 medium (cultivation without dilution) revealed late damage in the stem (precursor) cells of the skins of the animals. The proton fluxes employed in this experiment are representative of those occurring in major solar flares.

Do Intermediate Radiation Doses Contribute to Late Rectal Toxicity? An Analysis of Data From Radiation Therapy Oncology Group Protocol 94-06

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

Tucker, Susan L., E-mail: sltucker@mdanderson.org; Dong, Lei; Michalski, Jeff M.

2012-10-01

Purpose: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade {>=}2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. Methods and Materials: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportionmore » of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade {>=}2 late rectal toxicity. Results: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. Conclusions: There is no evidence from these data that intermediate doses influence the risk of Grade {>=}2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be {>=}75 Gy. It is hypothesized that cases of Grade {>=}2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a 'background' level of risk, likely due mainly to biological factors.« less

Anuran radiations and the evolution of tadpole morphospace

PubMed Central

Roelants, Kim; Haas, Alexander; Bossuyt, Franky

2011-01-01

Anurans (frogs and toads) are unique among land vertebrates in possessing a free-living larval stage that, parallel to adult frogs, diversified into an impressive range of ecomorphs. The tempo and mode at which tadpole morphology evolved through anuran history as well as its relationship to lineage diversification remain elusive. We used a molecular phylogenetic framework to examine patterns of morphological evolution in tadpoles in light of observed episodes of accelerated lineage diversification. Our reconstructions show that the expansion of tadpole morphospace during the basal anuran radiation in the Triassic/Early Jurassic was unparalleled by the basal neobatrachian radiation in the Late Jurassic/Early Cretaceous or any subsequent radiation in the Late Cretaceous/Early Tertiary. Comparative analyses of radiation episodes indicate that the slowdown of morphospace expansion was caused not only by a drop in evolutionary rate after the basal anuran radiation but also by an overall increase in homoplasy in the characters that did evolve during later radiations. The overlapping sets of evolving characters among more recent radiations may have enhanced tadpole diversity by creating unique combinations of homoplastic traits, but the lack of innovative character changes prevented the exploration of fundamental regions in morphospace. These complex patterns transcend the four traditionally recognized tadpole morphotypes and apply to most tissue types and body parts. PMID:21555583

Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

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

Olsen, Jeffrey R., E-mail: Jeffrey.R.Olsen@ucdenver.edu; Moughan, Jennifer; Myerson, Robert

Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structuremore » receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.« less

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

PubMed

Rubin, David T; Sandborn, William J; Bosworth, Brian; Zakko, Salam; Gordon, Glenn L; Sale, Mark E; Rolleri, Robert L; Golden, Pamela L; Barrett, Andrew C; Bortey, Enoch; Forbes, William P

2015-11-01

Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis. The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam. Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam. A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration. This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis.

Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

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

Sharma, Navesh K.; Li Tianyu; Chen, David Y.

Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dosemore » was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.« less

Treatment for Radiation-Induced Pulmonary Late Effects: Spoiled for Choice or Looking in the Wrong Direction?

PubMed Central

Williams, Jacqueline P.; Johnston, Carl J.; Finkelstein, Jacob N.

2010-01-01

Due to the radiosensitivity of the lung, toxic endpoints, in the form of radiation pneumonitis and pulmonary fibrosis, are relatively frequent outcomes following radiation treatment of thoracic neoplasms. Because of the potential lethal nature of these normal tissue reactions, they not only lead to quality-of-life issues in survivors, but also are deemed dose-limiting and thereby compromise treatment. The mitigation and treatment of lung normal tissue late effects has therefore been the goal of many investigations; however, the complexity of both the organ itself and its response to injury has resulted in little success. Nonetheless, current technology allows us to propose likely targets that are either currently being researched or should be considered in future studies. PMID:20583979

Space radiation risks to the central nervous system

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

2014-07-01

Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

Geometric Image Biomarker Changes of the Parotid Gland Are Associated With Late Xerostomia.

PubMed

van Dijk, Lisanne V; Brouwer, Charlotte L; van der Laan, Hans Paul; Burgerhof, Johannes G M; Langendijk, Johannes A; Steenbakkers, Roel J H M; Sijtsema, Nanna M

2017-12-01

To identify a surrogate marker for late xerostomia 12 months after radiation therapy (Xer 12m ), according to information obtained shortly after treatment. Differences in parotid gland (PG) were quantified in image biomarkers (ΔIBMs) before and 6 weeks after radiation therapy in 107 patients. By performing stepwise forward selection, ΔIBMs that were associated with Xer 12m were selected. Subsequently other variables, such as PG dose and acute xerostomia scores, were added to improve the prediction performance. All models were internally validated. Prediction of Xer 12m based on PG surface reduction (ΔPG-surface) was good (area under the receiver operating characteristic curve, 0.82). Parotid gland dose was related to ΔPG-surface (P<.001, R 2  = 0.27). The addition of acute xerostomia scores to the ΔPG-surface improved the prediction of Xer 12m significantly, and vice versa. The final model including ΔPG-surface and acute xerostomia had outstanding performance in predicting Xer 12m early after radiation therapy (area under the receiver operating characteristic curve, 0.90). Parotid gland surface reduction was associated with late xerostomia. The early posttreatment model with ΔPG-surface and acute xerostomia scores can be considered as a surrogate marker for late xerostomia. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Investigation of the radiological safety concerns and medical history of the late Joseph T. Harding, former employee of the Paducah Gaseous Diffusion Plant

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

Vallario, E.J.; Wolfe, H.R.

1981-03-01

An ex-employee's claims that inadequate enforcement of radiation safety regulations allowed excess radiation exposure thereby causing his deteriorating health was not substantiated by a thorough investigation.

Ionizing Radiation and the Ear

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

Borsanyi, Steven J.

The effects of ionizing radiation on the ears of 100 patients were studied in the course of treatment of malignant head and neck tumors by teleradiation using Co 60. Early changes consisted of radiation otitis media and a transient vasculitis of the vessels of the inner ear, resulting in hearing loss, tinnitus, and temporary recruitment. While no permanent changes were detected microscopically shortly after the completion of radiation in the cochlea or labyrinth, late changes sometimes occurred in the temporal bone as a result of an obliterating endarteritis. The late changes were separate entities caused primarily by obliterating endarteritis andmore » alterations in the collagen. Radiation affected the hearing of individuals selectively. When hearing threshold shift did occur, the shift was not great. The 4000 cps frequency showed a greater deficit in hearing capacity during the tests, while the area least affected appeared to be in the region of 2000 cps. The shift in speech reception was not significant and it was correlated with the over-all change in response to pure tones. Discrimination did not appear to be affected. Proper shielding of the ear with lead during radiation, when possible, eliminated most complications. (H.R.D.)« less

Combined effects of solar ultraviolet radiation and nutrients addition on growth, biomass and taxonomic composition of coastal marine phytoplankton communities of Patagonia.

PubMed

Marcoval, M Alejandra; Villafañe, Virginia E; Helbling, E Walter

2008-05-29

Experiments (6-8 days) were conducted during late summer, late fall and late winter, 2003 with waters collected off Bahía Nueva, Chubut, Argentina (42.7 degrees S, 65 degrees W) to determine the combined effects of solar ultraviolet radiation (UVR, 280-400 nm) and nutrient addition on phytoplankton communities. Samples were put in UVR-transparent containers and incubated under two radiation treatments: (a) Samples exposed to full solar radiation (PAB treatment, 280-400 nm) and (b) Samples exposed only to PAR (PAR treatment, 400-700 nm). At the beginning of the experiments, nutrients (i.e., NaPO(4)H(2) and NaNO(3)) were added to one set of samples from each radiation treatment (N cultures) whereas in the other set, nutrients remained at the concentration of the seawater. Chlorophyll a, biomass, UV-absorbing compounds and taxonomic composition were recorded throughout the experiments. N cultures always had significantly higher growth rates (P<0.05) than that in non-enriched cultures. At the beginning of experiments, phytoplankton communities were generally dominated by monads and flagellates but by the end, diatoms comprised the bulk of biomass, with only one to four taxa dominating, suggesting a selection towards more tolerant/less sensitive species. Over the experimental time frame, the observed taxonomic changes were mostly due to nutrient availability, and to a lesser extent to solar UVR exposure. Overall, the results indicate that environmental conditions (i.e., light history, nutrient concentration) together with the physiological status of the cells play a very important role at the time to assess the combined effect of nutrient addition and solar radiation on coastal phytoplankton assemblages from Patagonia.

Second cancers and late mortality in Australian children treated by allogeneic HSCT for haematological malignancy.

PubMed

Nelson, A S; Ashton, L J; Vajdic, C M; Le Marsney, R E; Daniels, B; Nivison-Smith, I; Wilcox, L; Dodds, A J; O'Brien, T A

2015-02-01

We examined risk of second cancer and late mortality in a population-based Australian cohort of 717 pediatric allogeneic stem cell transplant (HSCT) recipients treated for a malignant disease during 1982-2007. Record linkage with population-based death and cancer registries identified 17 second cancers at a median of 7.9 years post HSCT; thyroid cancer being the most common malignancy (n=8). The cumulative incidence of second cancer was 8.7% at follow-up, and second cancers occurred 20 times more often than in the general population (standardised incidence ratio 20.3, 95% confidence interval (CI)=12.6-32.7). Transplantation using radiation-based conditioning regimens was associated with increased second cancer risk. A total of 367 patients survived for at least 2 years post HSCT and of these 44 (12%) died at a median of 3.1 years after HSCT. Relapse was the most common cause of late mortality (n=32). The cumulative incidence of late mortality was 14.7%. The observed rate of late mortality was 36 times greater than in the matched general population (standardised mortality ratio 35.9, 95% CI=26.7-48.3). Recipients who relapsed or who had radiation-based conditioning regimens were at higher risk of late mortality. Second cancers and late mortality continue to be a risk for pediatric patients undergoing HSCT, and these results highlight the need for effective screening and survivorship programs.

[Lymphogranuloma venereum. An old disease in a new dress].

PubMed

de Roche, M; Sawatzki, M; Degen, L; Itin, P; Flückiger, U; Frei, R; Goldenberger, D

2011-05-01

Lymphogranuloma venereum is a sexually transmitted disease caused by Chlamydia trachomatis, serotypes L1, L2 and L3. The classical clinical manifestation is a painful inguinal lymphadenopathy, resulting without treatment in severe complications. Over the last years, however, the emergence of massive ulcerative proctitis has been observed, especially in men who have sex with men. Because the clinical symptoms are unspecific, Chlamydia trachomatis should actively be looked for. Reliable and rapid molecular tests have now been established to diagnose lymphogranuloma venereum. The therapeutic recommendation is tetracycline for 3 weeks. We present 5 cases to illustrate this disease.

The quantification of wound healing as a method to assess late radiation damage in primate skin exposed to high-energy protons

NASA Astrophysics Data System (ADS)

Cox, A. B.; Lett, J. T.

In an experiment examining the effects of space radiations on primates, different groups of rhesus monkeys (Macaca mulatta) were exposed to single whole-body doses of 32- or 55-MeV protons. Survivors of those exposures, together with age-matched controls, have been monitored continuously since 1964 and 1965. Late effects of nominal proton doses ranging from 2-6 Gray have been measured in vitro using skin fibroblasts from the animals. A logical extension of that study is reported here, and it involves observations of wound healing after 3-mm diameter dermal punches were removed from the ears (pinnae) of control and irradiated monkeys. Tendencies in the reduction of competence to repair cutaneous wound have been revealed by the initial examinations of animals that received doses greater than 2 Gy more than 2 decades earlier. These trends indicate that this method of assessing radiation damage to skin exposed to high-energy radiations warrants further study.

A basal thunnosaurian from Iraq reveals disparate phylogenetic origins for Cretaceous ichthyosaurs

PubMed Central

Fischer, Valentin; Appleby, Robert M.; Naish, Darren; Liston, Jeff; Riding, James B.; Brindley, Stephen; Godefroit, Pascal

2013-01-01

Cretaceous ichthyosaurs have typically been considered a small, homogeneous assemblage sharing a common Late Jurassic ancestor. Their low diversity and disparity have been interpreted as indicative of a decline leading to their Cenomanian extinction. We describe the first post-Triassic ichthyosaur from the Middle East, Malawania anachronus gen. et sp. nov. from the Early Cretaceous of Iraq, and re-evaluate the evolutionary history of parvipelvian ichthyosaurs via phylogenetic and cladogenesis rate analyses. Malawania represents a basal grade in thunnosaurian evolution that arose during a major Late Triassic radiation event and was previously thought to have gone extinct during the Early Jurassic. Its pectoral morphology appears surprisingly archaic, retaining a forefin architecture similar to that of its Early Jurassic relatives. After the initial latest Triassic radiation of early thunnosaurians, two subsequent large radiations produced lineages with Cretaceous representatives, but the radiation events themselves are pre-Cretaceous. Cretaceous ichthyosaurs therefore include distantly related lineages, with contrasting evolutionary histories, and appear more diverse and disparate than previously supposed. PMID:23676653

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

Bag, Satadru; Sahni, Varun; Viznyuk, Alexander

We obtain a closed system of equations for scalar perturbations in a multi-component braneworld. Our braneworld possesses a phantom-like equation of state at late times, w {sub eff} < −1, but no big-rip future singularity. In addition to matter and radiation, the braneworld possesses a new effective degree of freedom—the 'Weyl fluid' or 'dark radiation'. Setting initial conditions on super-Hubble spatial scales at the epoch of radiation domination, we evolve perturbations of radiation, pressureless matter and the Weyl fluid until the present epoch. We observe a gradual decrease in the amplitude of the Weyl-fluid perturbations after Hubble-radius crossing, which resultsmore » in a negligible effect of the Weyl fluid on the evolution of matter perturbations on spatial scales relevant for structure formation. Consequently, the quasi-static approximation of Koyama and Maartens provides a good fit to the exact results during the matter-dominated epoch. We find that the late-time growth of density perturbations on the brane proceeds at a faster rate than in ΛCDM. Additionally, the gravitational potentials Φ and Ψ evolve differently on the brane than in ΛCDM, for which Φ = Ψ. On the brane, by contrast, the ratio Φ/Ψ exceeds unity during the late matter-dominated epoch ( z ∼< 50). These features emerge as smoking gun tests of phantom brane cosmology and allow predictions of this scenario to be tested against observations of galaxy clustering and large-scale structure.« less

Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

1989-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Radiation protection guidelines for space missions

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

Fry, R.J.M.

1987-01-01

The original recommendations for radiation protection guidelines were made by the National Academy of Sciences in 1970. Since that time the US crews have become more diverse in their makeup and much has been learned about both radiation-induced cancer and other late effects. While far from adequate there is now some understanding of the risks that high-Z and -energy (HZE) particles pose. For these reasons it was time to reconsider the radiation protection guidelines for space workers. This task was undertaken recently by National Council on Radiation Protection (NCRP). 42 refs., 2 figs., 9 tabs.

An accelerated technique for irradiation of malignant canine nasal and paranasal sinus tumors.

PubMed

Adams, W M; Miller, P E; Vail, D M; Forrest, L J; MacEwen, E G

1998-01-01

Tumor and normal tissue response was assessed in 21 dogs with malignant nasal tumors given 42 Gy cobalt radiation in 9 or 10 fractions over 11 to 13 days. Local tumor/clinical relapse recurred in 68% of dogs, with a median relapse free interval (RFI) of 270 days. Median survival was 428 days. One year survival for all dogs was 60%. RFI and survival times are better than, or similar to, previous reports of dogs treated with radiotherapy only. Acute radiation effects were severe in one dog. Late effects were severe in six of 15 dogs (40%) with durable tumor control. Late effects included bilateral blindness (3), osteoradionecrosis (3), and seizures (1). These six dogs had a median survival of 705 days. Loss of vision occurred in at least one eye in nine dogs (47%). Tumor staging based on CT findings was predictive for survival duration. Tumor histology was not predictive of outcome. Labrador Retrievers were significantly over-represented. Despite comparable or improved tumor control and survival times provided by this accelerated protocol, relative to other radiotherapy reports, local failure remains the major cause of death, and late radiation effects can be severe in dogs with durable tumor control.

The evolutionary history of polycotylid plesiosaurians

NASA Astrophysics Data System (ADS)

Fischer, V.; Benson, R. B. J.; Druckenmiller, P. S.; Ketchum, H. F.; Bardet, N.

2018-03-01

Polycotylidae is a clade of plesiosaurians that appeared during the Early Cretaceous and became speciose and abundant early in the Late Cretaceous. However, this radiation is poorly understood. Thililua longicollis from the Middle Turonian of Morocco is an enigmatic taxon possessing an atypically long neck and, as originally reported, a series of unusual cranial features that cause unstable phylogenetic relationships for polycotylids. We reinterpret the holotype specimen of Thililua longicollis and clarify its cranial anatomy. Thililua longicollis possesses an extensive, foramina-bearing jugal, a premaxilla-parietal contact and carinated teeth. Phylogenetic analyses of a new cladistic dataset based on first-hand observation of most polycotylids recover Thililua and Mauriciosaurus as successive lineages at the base of the earliest Late Cretaceous polycotyline radiation. A new dataset summarizing the Bauplan of polycotylids reveals that their radiation produced an early burst of disparity during the Cenomanian-Turonian interval, with marked plasticity in relative neck length, but this did not arise as an ecological release following the extinction of ichthyosaurs and pliosaurids. This disparity vanished during and after the Turonian, which is consistent with a model of `early experimentation/late constraint'. Two polycotylid clades, Occultonectia clade nov. and Polycotylinae, survived up to the Maastrichtian, but with low diversity.

Long-term complications of definitive chemoradiotherapy for esophageal cancer using the classical method.

PubMed

Ito, Hitoshi; Itasaka, Satoshi; Sakanaka, Katsuyuki; Araki, Norio; Mizowaki, Takashi; Hiraoka, Masahiro

2017-01-01

Chemoradiation therapy is widely used to treat both inoperable and operable patients, and is less invasive than surgery. Although the number of long-term survivors who have received chemoradiation therapy is increasing, the long-term toxicity pattern and cumulative incidence of toxicity regarding this modality are poorly understood. Classically, chemoradiation therapy for esophageal cancer consists of an anterior-posterior field and a subsequent oblique boost field. We retrospectively analyzed patients who were treated with definitive chemoradiation therapy for esophageal cancer using this classical method from 1999 to 2008. For the assessment of toxicity, the National Cancer Institute Common Toxicity Criteria Version 3.0 was adopted. A total of 101 patients were analyzed. The median follow-up time was 16 months for all patients and 62 months for the surviving patients. Eleven patients experienced late toxicities of ≥Grade 3. Two patients died of late toxicities. The 3- and 5-year cumulative incidences for the first late cardiopulmonary toxicities of ≥Grade 3 were 17.4% and 20.8%, respectively. Cardiopulmonary effusions were observed within the first 3 years of completion of the initial treatment in seven out of eight patients. Sudden death and cardiac ischemia were observed over a 10-year period. Older age was found to be a risk factor for late toxicity after definitive chemoradiation therapy for esophageal cancer. Substantial toxicities were observed in patients who had received chemoradiation therapy for esophageal cancer using the classical method. To minimize the incidence of late toxicity, more sophisticated radiation techniques may be useful. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Data-driven management using quantitative metric and automatic auditing program (QMAP) improves consistency of radiation oncology processes.

PubMed

Yu, Naichang; Xia, Ping; Mastroianni, Anthony; Kolar, Matthew D; Chao, Samuel T; Greskovich, John F; Suh, John H

Process consistency in planning and delivery of radiation therapy is essential to maintain patient safety and treatment quality and efficiency. Ensuring the timely completion of each critical clinical task is one aspect of process consistency. The purpose of this work is to report our experience in implementing a quantitative metric and automatic auditing program (QMAP) with a goal of improving the timely completion of critical clinical tasks. Based on our clinical electronic medical records system, we developed a software program to automatically capture the completion timestamp of each critical clinical task while providing frequent alerts of potential delinquency. These alerts were directed to designated triage teams within a time window that would offer an opportunity to mitigate the potential for late completion. Since July 2011, 18 metrics were introduced in our clinical workflow. We compared the delinquency rates for 4 selected metrics before the implementation of the metric with the delinquency rate of 2016. One-tailed Student t test was used for statistical analysis RESULTS: With an average of 150 daily patients on treatment at our main campus, the late treatment plan completion rate and late weekly physics check were reduced from 18.2% and 8.9% in 2011 to 4.2% and 0.1% in 2016, respectively (P < .01). The late weekly on-treatment physician visit rate was reduced from 7.2% in 2012 to <1.6% in 2016. The yearly late cone beam computed tomography review rate was reduced from 1.6% in 2011 to <0.1% in 2016. QMAP is effective in reducing late completions of critical tasks, which can positively impact treatment quality and patient safety by reducing the potential for errors resulting from distractions, interruptions, and rush in completion of critical tasks. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

General relativistic radiative transfer code in rotating black hole space-time: ARTIST

NASA Astrophysics Data System (ADS)

Takahashi, Rohta; Umemura, Masayuki

2017-02-01

We present a general relativistic radiative transfer code, ARTIST (Authentic Radiative Transfer In Space-Time), that is a perfectly causal scheme to pursue the propagation of radiation with absorption and scattering around a Kerr black hole. The code explicitly solves the invariant radiation intensity along null geodesics in the Kerr-Schild coordinates, and therefore properly includes light bending, Doppler boosting, frame dragging, and gravitational redshifts. The notable aspect of ARTIST is that it conserves the radiative energy with high accuracy, and is not subject to the numerical diffusion, since the transfer is solved on long characteristics along null geodesics. We first solve the wavefront propagation around a Kerr black hole that was originally explored by Hanni. This demonstrates repeated wavefront collisions, light bending, and causal propagation of radiation with the speed of light. We show that the decay rate of the total energy of wavefronts near a black hole is determined solely by the black hole spin in late phases, in agreement with analytic expectations. As a result, the ARTIST turns out to correctly solve the general relativistic radiation fields until late phases as t ˜ 90 M. We also explore the effects of absorption and scattering, and apply this code for a photon wall problem and an orbiting hotspot problem. All the simulations in this study are performed in the equatorial plane around a Kerr black hole. The ARTIST is the first step to realize the general relativistic radiation hydrodynamics.

Late degeneration in rabbit tissues after irradiation by heavy ions

NASA Technical Reports Server (NTRS)

Lett, J. T.; Cox, A. B.; Keng, P. C.; Lee, A. C.; Su, C. M.; Bergtold, D. S.

1980-01-01

Results are presented for investigations of the late effects of heavy-ion irradiation on rabbit tissues which were undertaken to assess the hazards associated with the long-term exposure of humans to heavy ions in space during such activities as the construction of solar power stations or voyages to Mars. White rabbits approximately six weeks old were exposed to various doses of collimated beams of 400-MeV/n Ne ions, 570 MeV/n Ar ions and Co-60 gamma rays directed through both eyes, and the responses of the various tissues (hair follicles, skin, cornea, lens, retina, Harderian glands, bone and forebrain) were examined. Proliferating tissues are found to exhibit high damage levels in the early and late periods following irradiation, while terminally differentiating tissues repond to radiation most intensely in the late period, years after irradiation, with no intermediate recovery. The results obtained from rabbits are used to predict the occurrence of late tissue degeneration in the central nervous system, terminally differentiating systems and stem cells of humans one or more decades following exposure to radiation levels anticipated during long-duration space flights. The studies also indicate that tissues may be prematurely aged in the sense that tissue life spans may be shortened without the development of malignancies.

Effect of total body irradiation on late lung effects: hidden dangers.

PubMed

Johnston, Carl J; Manning, Casey; Hernady, Eric; Reed, Christina; Thurston, Sally W; Finkelstein, Jacob N; Williams, Jacqueline P

2011-08-01

In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge. C57BL/6J mice received total body irradiation (0.5-10 Gy) and were followed for 6-18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]). Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL]6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls. We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.

NCRP Program Area Committee 5: Environmental Radiation and Radioactive Waste Issues.

PubMed

Chen, S Y; Napier, Bruce

2016-02-01

Program Area Committee 5 of the National Council on Radiation Protection and Measurements (NCRP) focuses its activities on environmental radiation and radioactive waste issues. The Committee completed a number of reports in these subject areas, most recently NCRP Report No. 175, Decision Making for Late-Phase Recovery from Major Nuclear or Radiological Incidents. Historically this Committee addressed emerging issues of the nation pertaining to radioactivity or radiation in the environment or radioactive waste issues due either to natural origins or to manmade activities.

Phytosanitary irradiation of peach fruit moth (Lepidoptera: Carposinidae) in apple fruits

NASA Astrophysics Data System (ADS)

Zhan, Guoping; Li, Baishu; Gao, Meixu; Liu, Bo; Wang, Yuejin; Liu, Tao; Ren, Lili

2014-10-01

Peach fruit moth, Carposina sasakii Matsumura, is a serious pest of many pome and stone fruits and presents a quarantine problem in some export markets. It is widely distributed in pome fruit production areas in China, Japan, Korea, North Korea and the Far Eastern Federal District of Russia. In this investigation, gamma radiation dose-response tests were conducted with late eggs (5-d-old) and various larval stages, followed by large-scale confirmatory tests on the most tolerant stage in fruit, the fifth instar. The dose-response tests, with the target radiation dose of 20 (late eggs), 40, 60, 80, 100, 120, 140, and 160 Gy (late fifth instars in vitro) respectively applied to all stages, showed that the tolerance to radiation increased with increasing age and developmental stage. The fifth instar (most advanced instar in fruits) was determined to be the most tolerant stage requiring an estimated minimum absorbed dose of 208.6 Gy (95% CI: 195.0, 226.5 Gy) to prevent adult emergence at 99.9968% efficacy (95% confidence level). In the confirmatory tests, irradiation was applied to 30,850 late fifth instars in apple fruits with a target dose of 200 Gy (171.6-227.8 Gy measured), but only 4 deformed adults emerged that died 2 d afterwards without laying eggs. A dose of 228 Gy may be recommended as a phytosanitary irradiation treatment under ambient atmosphere for the control of peach fruit moth on all commodities with an efficacy of 99.9902% at 95% confidence level.

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L2) and D Lineages

PubMed Central

Somboonna, Naraporn; Wan, Raymond; Ojcius, David M.; Pettengill, Matthew A.; Joseph, Sandeep J.; Chang, Alexander; Hsu, Ray; Read, Timothy D.; Dean, Deborah

2011-01-01

ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2 and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomatis based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation. PMID:21540364

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case–control study in the UK

PubMed Central

Pallawela, S N S; Sullivan, A K; Macdonald, N; French, P; White, J; Dean, G; Smith, A; Winter, A J; Mandalia, S; Alexander, S; Ison, C; Ward, H

2014-01-01

Objective Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the UK in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. Design A prospective multicentre case–control study was conducted at six UK hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Methods Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Results Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. Conclusions This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. PMID:24687130

Meta-analysis of the association between appendiceal orifice inflammation and appendectomy and ulcerative colitis.

PubMed

Deng, Peng; Wu, Junchao

2016-07-01

This study aimed to investigate the relationship between appendiceal orifice inflammation (AOI) and appendectomy and ulcerative colitis (UC) by a meta-analysis. Databases were thoroughly searched for studies on AOI and UC up to January 2016. Three comparisons were performed: a) whether the previous appendectomy was a risk factor of UC; b) influence of appendectomy on UC courses; c) influence of AOI on UC severity. Odds ratios (ORs) and 95% confidence intervals (CIs) were the effects sizes. The merging of results and publication bias assessment were performed by using RevMan 5.3. Sensitivity analysis was conducted using Stata 12.0. Nineteen studies were selected in the present study. Results of comparison I showed that appendectomy was a protective factor of UC (OR = 0.44; 95% CI [0.30, 0.64]). Comparison II indicated appendectomy had no significant influence in the courses of UC (proctitis: OR = 1.03, 95% CI [0.74, 1.42]; left-sided colitis: OR = 1.01, 95% CI [0.73, 1.39]; pancolitis: OR = 0.92, 95% CI [0.59, 1.43]; colectomy: OR = 1.38, 95% CI [0.62, 3.04]). Comparison III indicated UC combined with AOI did not affect the courses of UC (proctitis: OR = 1.15, 95% CI [0.67, 1.98]; left-sided colitis: OR = 1.14, 95% CI [0.24, 5.42]; colectomy: OR = 0.36, 95% CI [0.10, 1.23]). Sensitivity analysis confirmed the robust of the results in the present study. In conclusion, this meta-analysis indicated appendectomy can reduce the risk of UC. But appendectomy or AOI had no influence on the severity of the disease and the effect of surgical treatment.

60Co contamination in recycled steel resulting in elevated civilian radiation doses: causes and challenges.

PubMed

Chang, W P; Chan, C C; Wang, J D

1997-09-01

Since late 1992, more than 100 building complexes containing public and private schools and nearly 1,000 apartments have been identified in Taiwan with elevated levels of gamma-radiation from construction steel contaminated with 60Co. Due to improper handling of 60Co contaminated scrap steel in late 1982 and 1983, contaminated construction materials have been widely distributed throughout the country. These contaminated construction materials have generated elevated radiation exposures to members of the public in Taiwan. As of early 1996, more than 4,000 people, including young students, have been identified as receiving more than 1 mSv y(-1) above the local background for up to 12 y. This report provides a detailed discussion of the sources of the 60Co contamination in construction steel, its discovery in the building complexes, and preliminary evaluation and remediation activities.

Dosimetric and clinical predictors for radiation-induced esophageal injury.

PubMed

Ahn, Sung-Ja; Kahn, Daniel; Zhou, Sumin; Yu, Xiaoli; Hollis, Donna; Shafman, Timothy D; Marks, Lawrence B

2005-02-01

To evaluate the clinical and three-dimensional dosimetric parameters associated with esophageal injury after radiotherapy (RT) for non-small-cell lung cancer. The records of 254 patients treated for non-small-cell lung cancer between 1992 and 2001 were reviewed. A variety of metrics describing the esophageal dose were extracted. The Radiation Therapy Oncology Group toxicity criteria for grading of esophageal injury were used. The median follow-up time for all patients was 43 months (range, 0.5-120 months). Logistic regression analysis, contingency table analyses, and Fisher's exact tests were used for statistical analysis. Acute toxicity occurred in 199 (78%) of 254 patients. For acute toxicity of Grade 2 or worse, twice-daily RT, age, nodal stage of N2 or worse, and most dosimetric parameters were predictive. Late toxicity occurred in 17 (7%) of 238 patients. The median and maximal time to the onset of late toxicity was 5 and 40 months after RT, respectively. Late toxicity occurred in 2%, 3%, 17%, 26%, and 100% of patients with acute Grade 0, 1, 2, 3, and 4 toxicity, respectively. For late toxicity, the severity of acute toxicity was most predictive. A variety of dosimetric parameters are predictive of acute and late esophageal injury. A strong correlation between the dosimetric parameters prevented a comparison between the predictive abilities of these metrics. The presence of acute injury was the most predictive factor for the development of late injury. Additional studies to define better the predictors of RT-induced esophageal injury are needed.

Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

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

Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org; Guerrero, Araceli; Maldonado, Xavier

Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research andmore » Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.« less

Effects of ionizing radiation on embryos of the tardigrade Milnesium cf. tardigradum at different stages of development.

PubMed

Beltrán-Pardo, Eliana; Jönsson, K Ingemar; Wojcik, Andrzej; Haghdoost, Siamak; Harms-Ringdahl, Mats; Bermúdez-Cruz, Rosa M; Bernal Villegas, Jaime E

2013-01-01

Tardigrades represent one of the most desiccation and radiation tolerant animals on Earth, and several studies have documented their tolerance in the adult stage. Studies on tolerance during embryological stages are rare, but differential effects of desiccation and freezing on different developmental stages have been reported, as well as dose-dependent effect of gamma irradiation on tardigrade embryos. Here, we report a study evaluating the tolerance of eggs from the eutardigrade Milnesium cf. tardigradum to three doses of gamma radiation (50, 200 and 500 Gy) at the early, middle, and late stage of development. We found that embryos of the middle and late developmental stages were tolerant to all doses, while eggs in the early developmental stage were tolerant only to a dose of 50 Gy, and showed a declining survival with higher dose. We also observed a delay in development of irradiated eggs, suggesting that periods of DNA repair might have taken place after irradiation induced damage. The delay was independent of dose for eggs irradiated in the middle and late stage, possibly indicating a fixed developmental schedule for repair after induced damage. These results show that the tolerance to radiation in tardigrade eggs changes in the course of their development. The mechanisms behind this pattern are unknown, but may relate to changes in mitotic activities over the embryogenesis and/or to activation of response mechanisms to damaged DNA in the course of development.

Effects of Ionizing Radiation on Embryos of the Tardigrade Milnesium cf. tardigradum at Different Stages of Development

PubMed Central

Beltrán-Pardo, Eliana; Jönsson, K. Ingemar; Wojcik, Andrzej; Haghdoost, Siamak; Harms-Ringdahl, Mats; Bermúdez-Cruz, Rosa M.; Bernal Villegas, Jaime E.

2013-01-01

Tardigrades represent one of the most desiccation and radiation tolerant animals on Earth, and several studies have documented their tolerance in the adult stage. Studies on tolerance during embryological stages are rare, but differential effects of desiccation and freezing on different developmental stages have been reported, as well as dose-dependent effect of gamma irradiation on tardigrade embryos. Here, we report a study evaluating the tolerance of eggs from the eutardigrade Milnesium cf. tardigradum to three doses of gamma radiation (50, 200 and 500 Gy) at the early, middle, and late stage of development. We found that embryos of the middle and late developmental stages were tolerant to all doses, while eggs in the early developmental stage were tolerant only to a dose of 50 Gy, and showed a declining survival with higher dose. We also observed a delay in development of irradiated eggs, suggesting that periods of DNA repair might have taken place after irradiation induced damage. The delay was independent of dose for eggs irradiated in the middle and late stage, possibly indicating a fixed developmental schedule for repair after induced damage. These results show that the tolerance to radiation in tardigrade eggs changes in the course of their development. The mechanisms behind this pattern are unknown, but may relate to changes in mitotic activities over the embryogenesis and/or to activation of response mechanisms to damaged DNA in the course of development. PMID:24039737

2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

NASA Technical Reports Server (NTRS)

2014-01-01

The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

Reconstruction of late craniofacial deformities after irradiation of the head and face during childhood

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

Cohen, S.R.; Bartlett, S.P.; Whitaker, L.A.

1990-08-01

Little is known about the results of surgical management of late craniofacial abnormalities arising after irradiation of the head and face for treatment of childhood cancers. The clinical records of 10 children (4 males and 6 females) who received 4500 to 6500 rads (mean 5160 rads) of craniofacial radiation between birth and 8 years of age (mean 5 years) and who subsequently had reconstructive surgery were reviewed. Six of the 10 patients received orbital radiation, 3 received maxillary-midfacial radiation, and 1 patient underwent radiation to the frontal bone. Histologic tumor types included retinoblastoma (4), rhabdomyosarcoma (3), Ewing's sarcoma (2), andmore » neurofibrosarcoma (1). In addition to radiation, 7 of the 10 patients underwent surgical resection or debulking of their tumors and 6 received adjuvant chemotherapy. All patients presented from 4 to 20 years after treatment (mean 10 years) with varying, but severe degrees of soft-tissue and bony hypoplasia of the irradiated territories. Onlay bone grafting with soft-tissue reconstruction by a combination of local pedicle flaps and dermal-fat grafts was initially performed in 9 patients, and an occipitoparietal bone-flap switch procedure was done in 1 patient. Late follow-up ranged from 11 months to 7.5 years (mean 34 months). A total of 8 secondary procedures were necessary in 4 of the 10 patients (40 percent). Of these 4 patients, major revisions were performed in 3 and minor adjustments in 1. In addition, 2 patients in whom secondary procedures had not been done would benefit from further reconstruction. Therapy for cancer of the head and face during childhood has profound and ongoing effects on the growth of soft tissue and bone.« less

Radiation dose reduction in abdominal computed tomography during the late hepatic arterial phase using a model-based iterative reconstruction algorithm: how low can we go?

PubMed

Husarik, Daniela B; Marin, Daniele; Samei, Ehsan; Richard, Samuel; Chen, Baiyu; Jaffe, Tracy A; Bashir, Mustafa R; Nelson, Rendon C

2012-08-01

The aim of this study was to compare the image quality of abdominal computed tomography scans in an anthropomorphic phantom acquired at different radiation dose levels where each raw data set is reconstructed with both a standard convolution filtered back projection (FBP) and a full model-based iterative reconstruction (MBIR) algorithm. An anthropomorphic phantom in 3 sizes was used with a custom-built liver insert simulating late hepatic arterial enhancement and containing hypervascular liver lesions of various sizes. Imaging was performed on a 64-section multidetector-row computed tomography scanner (Discovery CT750 HD; GE Healthcare, Waukesha, WI) at 3 different tube voltages for each patient size and 5 incrementally decreasing tube current-time products for each tube voltage. Quantitative analysis consisted of contrast-to-noise ratio calculations and image noise assessment. Qualitative image analysis was performed by 3 independent radiologists rating subjective image quality and lesion conspicuity. Contrast-to-noise ratio was significantly higher and mean image noise was significantly lower on MBIR images than on FBP images in all patient sizes, at all tube voltage settings, and all radiation dose levels (P < 0.05). Overall image quality and lesion conspicuity were rated higher for MBIR images compared with FBP images at all radiation dose levels. Image quality and lesion conspicuity on 25% to 50% dose MBIR images were rated equal to full-dose FBP images. This phantom study suggests that depending on patient size, clinically acceptable image quality of the liver in the late hepatic arterial phase can be achieved with MBIR at approximately 50% lower radiation dose compared with FBP.

Long-Term Results of Concomitant Boost Radiation Plus Concurrent Cisplatin for Advanced Head and Neck Carcinomas: A Phase II Trial of the Radiation Therapy Oncology Group (RTOG 99-14)

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

Garden, Adam S.; Harris, Jonathan M.S.; Trotti, Andy

2008-08-01

Purpose: The feasibility of combining concomitant boost-accelerated radiation regimen (AFX-C) with cisplatin was previously demonstrated in this Phase II trial. This article reports the long-term toxicity, relapse patterns, and survival in patients with advanced head and neck carcinoma. Methods and Materials: Between April and November 2000, 84 patients with Stage III-IV HNC were enrolled, and 76 patients were analyzable. Radiation consisted of 72 Gy over 6 weeks. Cisplatin dose was 100 mg/m{sup 2} on Days 1 and 22. Tumor and clinical status were assessed, and acute-late toxicities were graded. Results: The median follow-up for surviving patients is 4.3 years. Themore » 2- and 4-year locoregional failure rates were 33% and 36%, respectively, and the 2- and 4-year survival rates were 70% and 54%, respectively. The worst overall late Grade 3 or 4 toxicity rate was 42%. The prevalence rates of a gastrostomy at any time during follow-up, at 12 months, and at 48 months were 83%, 41%, and 17%, respectively. Five of 36 patients (14%) alive and without disease at last follow-up were gastrostomy-tube dependent. Conclusion: These data of long-term follow-up of patients treated with AFX-C with cisplatin show encouraging results with regard to locoregional disease control and survival, with few recurrences after 2 years. The late toxicity rates are relatively high. However, although prolonged dysphagia was noted in our preliminary report, its prevalence does decreased over time. A Phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin has completed accrual.« less

Recurrent gastric perforation as a late complication of radiotherapy for mucosa-associated lymphoid tissue lymphoma of the stomach.

PubMed

Otsuka, Taiga; Noda, Takahiro; Yokoo, Masako; Ibaraki, Kazuo

2008-01-01

Radiation therapy can be used to treat Helicobacter pylori-negative or eradication-refractory extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of the stomach. We report a case of gastric perforation which occurred more than 1 year after the completion of radiotherapy for H. pylori eradication-refractory gastric MALT lymphoma, and then recurred shortly afterwards. This was considered to be a late complication of radiation toxicity. Although gastric perforation due to radiotherapy has been reported very rarely in the past, even in advanced disease, this case shows that perforation can develop in patients with superficial disease and can relapse.

Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer

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

Lewis, Stephen L.; Patel, Pretesh; Song, Haijun

2016-03-01

Purpose: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. Methods and Materials: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities weremore » scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. Results: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). Conclusions: The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.« less

Radiation-Induced Chromosomal Aberrations and Immunotherapy: Micronuclei, Cytosolic DNA, and Interferon-Production Pathway.

PubMed

Durante, Marco; Formenti, Silvia C

2018-01-01

Radiation-induced chromosomal aberrations represent an early marker of late effects, including cell killing and transformation. The measurement of cytogenetic damage in tissues, generally in blood lymphocytes, from patients treated with radiotherapy has been studied for many years to predict individual sensitivity and late morbidity. Acentric fragments are lost during mitosis and create micronuclei (MN), which are well correlated to cell killing. Immunotherapy is rapidly becoming a most promising new strategy for metastatic tumors, and combination with radiotherapy is explored in several pre-clinical studies and clinical trials. Recent evidence has shown that the presence of cytosolic DNA activates immune response via the cyclic GMP-AMP synthase/stimulator of interferon genes pathway, which induces type I interferon transcription. Cytosolic DNA can be found after exposure to ionizing radiation either as MN or as small fragments leaking through nuclear envelope ruptures. The study of the dependence of cytosolic DNA and MN on dose and radiation quality can guide the optimal combination of radiotherapy and immunotherapy. The role of densely ionizing charged particles is under active investigation to define their impact on the activation of the interferon pathway.

Cisplatin radiosensitizes radioresistant human mesenchymal stem cells.

PubMed

Rühle, Alexander; Perez, Ramon Lopez; Glowa, Christin; Weber, Klaus-Josef; Ho, Anthony D; Debus, Jürgen; Saffrich, Rainer; Huber, Peter E; Nicolay, Nils H

2017-10-20

Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced. The increased cisplatin-mediated radiosensitivity was associated with a cell cycle shift of MSCs towards the radiosensitive G2/M phase and increased residual DNA double-strand breaks. These data demonstrate for the first time a dose-dependent radiosensitization effect of MSCs by cisplatin. Clinically, the observed increase in radiation sensitivity and subsequent loss of regenerative MSCs may contribute to the often severe late toxicities observed after cisplatin-based chemo-radiotherapy in cancer patients.

Lymphogranuloma venereum detected from the pharynx in four London men who have sex with men.

PubMed

Dosekun, O; Edmonds, S; Stockwell, S; French, P; White, J A

2013-06-01

Lymphogranuloma venereum (LGV) is an established cause of proctitis in men who have sex with men (MSM). Currently in the UK, testing for pharyngeal Chlamydia trachomatis (CT) is not routine, and LGV typing is usually only performed in patients with anorectal symptoms. We report four cases where LGV-associated CT DNA was detected from the pharynx in MSM, demonstrating that nucleic acid amplification testing (NAAT) can be used for detecting and typing pharyngeal CT infection. These cases also highlight other possible routes of infection for LGV, and add to the broad spectrum of clinical presentations associated with this infection.

Group A beta-hemolytic streptococcal hemorrhagic colitis complicated with pharyngitis and impetigo.

PubMed

Isozaki, Atsushi; Matsubara, Keiko; Yui, Takako; Kobayashi, Kenji; Kawano, Yutaka

2007-12-01

A 6-year-old boy with bloody diarrhea was diagnosed with group A beta-hemolytic streptococcal hemorrhagic colitis. Complications included pharyngitis and impetigo, both caused by the same organisms. In addition to being isolated from stools, Streptococcus pyogenes was also isolated from skin lesions. Furthermore, a rapid group A streptococcal antigen test by throat swab was also positive. Hemorrhagic colitis caused by group A beta-hemolytic streptococcus is extremely rare, and much rarer are its complications with pharyngitis and impetigo. Compared with findings in reports of group A beta-hemolytic streptococcal proctitis and perianal and perineal diseases, this case suggests a distinct pathogenesis for hemorrhagic colitis.

Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates

PubMed Central

Andrews, Rachel N.; Metheny-Barlow, Linda J.; Peiffer, Ann M.; Hanbury, David B.; Tooze, Janet A.; Bourland, J. Daniel; Hampson, Robert E.; Deadwyler, Samuel A.; Cline, J. Mark

2017-01-01

Andrews, R. N., Metheny-Barlow, L. J., Peiffer, A. M., Hanbury, D. B., Tooze, J. A., Bourland, J. D., Hampson, R. E., Deadwyler, S. A. and Cline, J. M. Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates. Radiat. Res. 187, 599–611 (2017). Fractionated whole-brain irradiation (fWBI) is a mainstay of treatment for patients with intracranial neoplasia; however late-delayed radiation-induced normal tissue injury remains a major adverse consequence of treatment, with deleterious effects on quality of life for affected patients. We hypothesize that cerebrovascular injury and remodeling after fWBI results in ischemic injury to dependent white matter, which contributes to the observed cognitive dysfunction. To evaluate molecular effectors of radiation-induced brain injury (RIBI), real-time quantitative polymerase chain reaction (RT-qPCR) was performed on the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46), hippocampus and temporal white matter of 4 male Rhesus macaques (age 6–11 years), which had received 40 Gray (Gy) fWBI (8 fractions of 5 Gy each, twice per week), and 3 control comparators. All fWBI animals developed neurologic impairment; humane euthanasia was elected at a median of 6 months. Radiation-induced brain injury was confirmed histopathologically in all animals, characterized by white matter degeneration and necrosis, and multifocal cerebrovascular injury consisting of perivascular edema, abnormal angiogenesis and perivascular extracellular matrix deposition. Herein we demonstrate that RIBI is associated with white matter-specific up-regulation of hypoxia-associated lactate dehydrogenase A (LDHA) and that increased gene expression of fibronectin 1 (FN1), SERPINE1 and matrix metalloprotease 2 (MMP2) may contribute to cerebrovascular remodeling in late-delayed RIBI. Additionally, vascular stability and maturation associated tumor necrosis super family member 15 (TNFSF15) and vascular endothelial growth factor beta (VEGFB) mRNAs were increased within temporal white matter. We also demonstrate that radiation-induced brain injury is associated with decreases in white matter-specific expression of neurotransmitter receptors SYP, GRIN2A and GRIA4. We additionally provide evidence that macrophage/microglial mediated neuroinflammation may contribute to RIBI through increased gene expression of the macrophage chemoattractant CCL2 and macrophage/ microglia associated CD68. Global patterns in cerebral gene expression varied significantly between regions examined (P < 0.0001, Friedman’s test), with effects most prominent within cerebral white matter. PMID:28398880

Reirradiation of head and neck cancer: Long-term disease control and toxicity.

PubMed

Bots, Wouter T C; van den Bosch, Sven; Zwijnenburg, Ellen M; Dijkema, Tim; van den Broek, Guido B; Weijs, Willem L J; Verhoef, Lia C G; Kaanders, Johannes H A M

2017-06-01

The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122-1130, 2017. © 2017 The Authors Head & Neck Published by Wiley Periodicals, Inc.

The Origin and Early Radiation of Archosauriforms: Integrating the Skeletal and Footprint Record.

PubMed

Bernardi, Massimo; Klein, Hendrik; Petti, Fabio Massimo; Ezcurra, Martín D

2015-01-01

We present a holistic approach to the study of early archosauriform evolution by integrating body and track records. The ichnological record supports a Late Permian-Early Triassic radiation of archosauriforms not well documented by skeletal material, and new footprints from the Upper Permian of the southern Alps (Italy) provide evidence for a diversity not yet sampled by body fossils. The integrative study of body fossil and footprint data supports the hypothesis that archosauriforms had already undergone substantial taxonomic diversification by the Late Permian and that by the Early Triassic archosauromorphs attained a broad geographical distribution over most parts of Pangea. Analysis of body size, as deduced from track size, suggests that archosauriform average body size did not change significantly from the Late Permian to the Early Triassic. A survey of facies yielding both skeletal and track record indicate an ecological preference for inland fluvial (lacustrine) environments for early archosauromorphs. Finally, although more data is needed, Late Permian chirotheriid imprints suggest a shift from sprawling to erect posture in archosauriforms before the end-Permian mass extinction event. We highlight the importance of approaching palaeobiological questions by using all available sources of data, specifically through integrating the body and track fossil record.

The Origin and Early Radiation of Archosauriforms: Integrating the Skeletal and Footprint Record

PubMed Central

Bernardi, Massimo; Klein, Hendrik; Petti, Fabio Massimo; Ezcurra, Martín D.

2015-01-01

We present a holistic approach to the study of early archosauriform evolution by integrating body and track records. The ichnological record supports a Late Permian–Early Triassic radiation of archosauriforms not well documented by skeletal material, and new footprints from the Upper Permian of the southern Alps (Italy) provide evidence for a diversity not yet sampled by body fossils. The integrative study of body fossil and footprint data supports the hypothesis that archosauriforms had already undergone substantial taxonomic diversification by the Late Permian and that by the Early Triassic archosauromorphs attained a broad geographical distribution over most parts of Pangea. Analysis of body size, as deduced from track size, suggests that archosauriform average body size did not change significantly from the Late Permian to the Early Triassic. A survey of facies yielding both skeletal and track record indicate an ecological preference for inland fluvial (lacustrine) environments for early archosauromorphs. Finally, although more data is needed, Late Permian chirotheriid imprints suggest a shift from sprawling to erect posture in archosauriforms before the end-Permian mass extinction event. We highlight the importance of approaching palaeobiological questions by using all available sources of data, specifically through integrating the body and track fossil record. PMID:26083612

Plio-Pleistocene climate sensitivity evaluated using high-resolution CO2 records

NASA Astrophysics Data System (ADS)

Martínez-Botí, M. A.; Foster, G. L.; Chalk, T. B.; Rohling, E. J.; Sexton, P. F.; Lunt, D. J.; Pancost, R. D.; Badger, M. P. S.; Schmidt, D. N.

2015-02-01

Theory and climate modelling suggest that the sensitivity of Earth's climate to changes in radiative forcing could depend on the background climate. However, palaeoclimate data have thus far been insufficient to provide a conclusive test of this prediction. Here we present atmospheric carbon dioxide (CO2) reconstructions based on multi-site boron-isotope records from the late Pliocene epoch (3.3 to 2.3 million years ago). We find that Earth's climate sensitivity to CO2-based radiative forcing (Earth system sensitivity) was half as strong during the warm Pliocene as during the cold late Pleistocene epoch (0.8 to 0.01 million years ago). We attribute this difference to the radiative impacts of continental ice-volume changes (the ice-albedo feedback) during the late Pleistocene, because equilibrium climate sensitivity is identical for the two intervals when we account for such impacts using sea-level reconstructions. We conclude that, on a global scale, no unexpected climate feedbacks operated during the warm Pliocene, and that predictions of equilibrium climate sensitivity (excluding long-term ice-albedo feedbacks) for our Pliocene-like future (with CO2 levels up to maximum Pliocene levels of 450 parts per million) are well described by the currently accepted range of an increase of 1.5 K to 4.5 K per doubling of CO2.

Dosimetric and clinical predictors of radiation-induced lung toxicity in esophageal carcinoma.

PubMed

Zhu, Shu-Chai; Shen, Wen-Bin; Liu, Zhi-Kun; Li, Juan; Su, Jing-Wei; Wang, Yu-Xiang

2011-01-01

Radiation-induced lung toxicity occurs frequently in patients with esophageal carcinoma. This study aims to evaluate the clinical and three-dimensional dosimetric parameters associated with lung toxicity after radiotherapy for esophageal carcinoma. The records of 56 patients treated for esophageal carcinoma were reviewed. The Radiation Therapy Oncology Group criteria for grading of lung toxicity were followed. Spearman's correlation test, the chi-square test and logistic regression analyses were used for statistical analysis. Ten of the 56 patients developed acute toxicity. The toxicity grades were grade 2 in 7 patients and grade 3 in 3 patients; none of the patients developed grade 4 or worse toxicity. One case of toxicity occurred during radiotherapy and 9 occurred 2 weeks to 3 months after radiotherapy. The median time was 2.0 months after radiotherapy. Fourteen patients developed late irradiated lung injury, 3 after 3.5 months, 7 after 9 months, and 4 after 14 months. Radiographic imaging demonstrated patchy consolidation (n = 5), atelectasis with parenchymal distortion (n = 6), and solid consolidation (n = 3). For acute toxicity, the irradiated esophageal volume, number of fields, and most dosimetric parameters were predictive. For late toxicity, chemotherapy combined with radiotherapy and other dosimetric parameters were predictive. No obvious association between the occurrence of acute and late injury was observed. The percent of lung tissue receiving at least 25 Gy (V25), the number of fields, and the irradiated length of the esophagus can be used as predictors of the risk of acute toxicity. Lungs V30, as well as chemotherapy combined with radiotherapy, are predictive of late lung injury.

Lymphogranuloma venereum diagnoses among men who have sex with men in the U.K.: interpreting a cross-sectional study using an epidemic phase-specific framework.

PubMed

Hughes, Gwenda; Alexander, Sarah; Simms, Ian; Conti, Stefano; Ward, Helen; Powers, Cassandra; Ison, Catherine

2013-11-01

To investigate the drivers behind the epidemic expansion of lymphogranuloma venereum (LGV) cases in late 2009 to help inform infection control. An epidemic curve of all LGV diagnoses between 2003 and mid-2012 was plotted and divided into the initial detection period, and endemic, growth and hyperendemic phases. Detailed clinical and behavioural data were collected and logistic regression was used to compare the characteristics of diagnoses made during the growth and endemic phases. Between April 2003 and June 2012, 2138 cases of LGV were diagnosed. Enhanced surveillance data were available for 1370 of whom 1353 were men who have sex with men (MSM). 98% of MSM presented with proctitis, 82% were HIV positive, 20% were hepatitis C virus (HCV) antibody positive, and 67% lived in London. Growth phase cases (n=488) were more likely to report meeting sexual contacts at sex parties (11% vs. 6%, p=0.014), unprotected receptive or insertive oral intercourse (93% vs. 86%, p=0.001; 92% vs. 85%, p=0.001) and sharing sex toys (8% vs 4%; p=0.011), and to be diagnosed HIV positive (86% vs. 80%; p=0.014), than endemic phase cases (n=423). Unprotected receptive anal intercourse was equally likely to be reported in both phases (71% vs. 73%). After adjustment, cases in the growth phase were more likely to meet new contacts at sex parties (p=0.031) and be HIV positive (p=0.045). Rapid epidemic growth coincided with an intensification of unprotected sexual activity among a core population of HIV-positive MSM. Efforts to develop innovative interventions for this hard-to-reach population are needed.

Dosimetric analysis of imaging changes following pulmonary stereotactic body radiation therapy.

PubMed

Prendergast, Brendan M; Bonner, James A; Popple, Richard A; Spencer, Sharon A; Fiveash, John B; Keene, Kimberly S; Cerfolio, Robert J; Minnich, Douglas J; Dobelbower, Michael C

2011-02-01

The aim of this study was to determine whether late patterns of pulmonary fibrosis are related to specific radiation doses administered during thoracic stereotactic body radiation therapy (SBRT). The records of all patients treated with SBRT for either pulmonary metastases or inoperable primary lung tumours at the University of Alabama at Birmingham from November 2005 to July 2008 were reviewed. Patients selected for analysis had diagnostic chest computed tomography (CT) scans acquired at least 180 days after completion of therapy. CT scans acquired at follow-up were co-registered with the original treatment planning CT scans for 12 eligible patients (17 lesions), and late-occurring pulmonary imaging abnormalities (IAs) were contoured. Dosimetric parameters analysed include D(80) , D(90) , V(18) and V(prescription dose) of the IA and V(14) and V(18) of the lung. Late pulmonary IAs were identified in 11 treated areas from nine patients. Late IAs could not be identified in six treated areas from three patients secondary to emphysema, tumour progression and severe atelectasis, respectively. The mean doses to 80% (D(80) ) and 90% (D(90) ) of the IAs were 18.4 and 14.5 Gy, respectively (ranges: 5.6-27.8 and 3.3-22.4 Gy). On average, 79.4% (range: 45.6-97.5%) of the IA received at least 18 Gy, while an average of 19.3% (range: 0.2-42.2%) received the prescription dose. On average, only 4.2% (range: 1.1-7.8%) of the lungs received 18 Gy. Imaging abnormalities consistent with pulmonary fibrosis are common after SBRT and are well approximated by the 18 Gy isodose distribution. The clinical ramification of these findings should be evaluated in future studies. © 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.

Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone oligometastases.

PubMed

Owen, Dawn; Laack, Nadia N; Mayo, Charles S; Garces, Yolanda I; Park, Sean S; Bauer, Heather J; Nelson, Kathryn; Miller, Robert W; Brown, Paul D; Olivier, Kenneth R

2014-01-01

Stereotactic body radiation therapy (SBRT) is being applied more widely for oligometastatic disease. This technique is now being used for non-spine bony metastases in addition to liver, spine, and lung. However, there are few studies examining the toxicity and outcomes of SBRT for non-spine bone metastases. Between 2008 and 2012, 74 subjects with oligometastatic non-spine bony metastases of varying histologies were treated at the Mayo Clinic with SBRT. A total of 85 non-spine bony sites were treated. Median local control, overall survival, and progression-free survival were described. Acute toxicity (defined as toxicity <90 days) and late toxicity (defined as toxicity ≥90 days) were reported and graded as per standardized Common Toxicity Criteria for Adverse Events 4.0 criteria. The median age of patients treated was 60 years. The most common histology was prostate cancer (31%) and most patients had fewer than 3 sites of disease at the time of simulation (64%). Most of the non-spine bony sites lay within the pelvis (65%). Dose and fractionation varied but the most common prescription was 24 Gy/1 fraction. Local recurrence occurred in 7 patients with a median time to failure of 2.8 months. Local control was 91.8% at 1 year. With a median follow-up of 7.6 months, median SBRT specific overall survival and progression-free survival were 9.3 months and 9.7 months, respectively. Eighteen patients developed acute toxicity (mostly grade 1 and 2 fatigue and acute pain flare); 9 patients developed grade 1-2 late toxicities. Two patients developed pathologic fractures but both were asymptomatic. There were no late grade 3 or 4 toxicities. Stereotactic body radiation therapy is a feasible and tolerable treatment for non-spine bony metastases. Longer follow-up will be needed to accurately determine late effects. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Rectal compliance as a routine measurement: extreme volumes have direct clinical impact and normal volumes exclude rectum as a problem.

PubMed

Felt-Bersma, R J; Sloots, C E; Poen, A C; Cuesta, M A; Meuwissen, S G

2000-12-01

The clinical impact of rectal compliance and sensitivity measurement is not clear. The aim of this study was to measure the rectal compliance in different patient groups compared with controls and to establish the clinical effect of rectal compliance. Anorectal function tests were performed in 974 consecutive patients (284 men). Normal values were obtained from 24 controls. Rectal compliance measurement was performed by filling a latex rectal balloon with water at a rate of 60 ml per minute. Volume and intraballoon pressure were measured. Volume and pressure at three sensitivity thresholds were recorded for analysis: first sensation, urge, and maximal toleration. At maximal toleration, the rectal compliance (volume/pressure) was calculated. Proctoscopy, anal manometry, anal mucosal sensitivity, and anal endosonography were also performed as part of our anorectal function tests. No effect of age or gender was observed in either controls or patients. Patients with fecal incontinence had a higher volume at first sensation and a higher pressure at maximal toleration (P = 0.03), the presence of a sphincter defect or low or normal anal pressures made no difference. Patients with constipation had a larger volume at first sensation and urge (P < 0.0001 and P < 0.01). Patients with a rectocele had a larger volume at first sensation (P = 0.004). Patients with rectal prolapse did not differ from controls; after rectopexy, rectal compliance decreased (P < 0.0003). Patients with inflammatory bowel disease had a lower rectal compliance, most pronounced in active proctitis (P = 0.003). Patients with ileoanal pouches also had a lower compliance (P < 0.0001). In the 17 patients where a maximal toleration volume < 60 ml was found, 11 had complaints of fecal incontinence, and 6 had a stoma. In 31 patients a maximal toleration volume between 60 and 100 ml was found; 12 patients had complaints of fecal incontinence, and 6 had a stoma. Proctitis or pouchitis was the main cause for a small compliance. All 29 patients who had a maximal toleration volume > 500 ml had complaints of constipation. No correlation between rectal and anal mucosal sensitivity was found. Rectal compliance measurement with a latex balloon is easily feasible. In this series of 974 patients, some patient groups showed an abnormal rectal visceral sensitivity and compliance, but there was an overlap with controls. Rectal compliance measurement gave a good clinical impression about the contribution of the rectum to the anorectal problem. Patients with proctitis and pouchitis had the smallest rectal compliance. A maximal toleration volume < 60 ml always led to fecal incontinence, and stomas should be considered for such patients. A maximal toleration volume > 500 ml was only seen in constipated patients, and therapy should be given to prevent further damage to the pelvic floor. Values close to or within the normal range rule out the rectum as an important factor in the anorectal problem of the patient.

AlGaN UV LED and Photodiodes Radiation Hardness and Space Qualifications and Their Applications in Space Science and High Energy Density Physics

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

Sun, K. X.

2011-05-31

This presentation provides an overview of robust, radiation hard AlGaN optoelectronic devices and their applications in space exploration & high energy density physics. Particularly, deep UV LED and deep UV photodiodes are discussed with regard to their applications, radiation hardness and space qualification. AC charge management of UV LED satellite payload instruments, which were to be launched in late 2012, is covered.

Brain dose-sparing radiotherapy techniques for localized intracranial germinoma: Case report and literature review of modern irradiation.

PubMed

Leung, H W C; Chan, A L F; Chang, M B

2016-05-01

We examined the effects of intensity-modulated radiation therapy with dose-sparing and avoidance technique on a pediatric patient with localized intracranial germinoma. We also reviewed the literature regarding modern irradiation techniques in relation to late neurocognitive sequelae. A patient with a localized intracranial germinoma in the third ventricle anterior to the pineal gland received a dose-sparing intensity-modulated radiation therapy. The planning was compared to the radiation oncologist's guide of organs at risk and dose constraints for dosimetric analyses. The patient received radiation therapy alone. The total dose was 54Gy delivered in 2.0Gy fractions to the primary tumour and 37Gy in 1.4Gy fractions to whole ventricles using a dose-sculpting plan. Dosimetry analyses showed that dose-sparing intensity-modulated radiation therapy delivered reduced doses to the whole brain, temporal lobes, hippocampi, cochleae, and optic nerves. With a follow-up of 22 months, failure-free survival was 100% for the patient and no adverse events during radiation treatment process. Intensity-modulated radiation therapy with dose sparing and avoidance technique can spare the limbic circuit, central nervous system, and hippocampus for pineal germ cell tumours. This technique reduces the integral dose delivered to the uninvolved normal brain tissues and may reduce late neurocognitive sequelae caused by cranial radiotherapy. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Radiation dose-volume effects in the esophagus.

PubMed

Werner-Wasik, Maria; Yorke, Ellen; Deasy, Joseph; Nam, Jiho; Marks, Lawrence B

2010-03-01

Publications relating esophageal radiation toxicity to clinical variables and to quantitative dose and dose-volume measures derived from three-dimensional conformal radiotherapy for non-small-cell lung cancer are reviewed. A variety of clinical and dosimetric parameters have been associated with acute and late toxicity. Suggestions for future studies are presented. Copyright 2010 Elsevier Inc. All rights reserved.

Singular F(R) cosmology unifying early- and late-time acceleration with matter and radiation domination era

NASA Astrophysics Data System (ADS)

Odintsov, S. D.; Oikonomou, V. K.

2016-06-01

We present some cosmological models which unify the late- and early-time acceleration eras with the radiation and the matter domination era, and we realize the cosmological models by using the theoretical framework of F(R) gravity. Particularly, the first model unifies the late- and early-time acceleration with the matter domination era, and the second model unifies all the evolution eras of our Universe. The two models are described in the same way at early and late times, and only the intermediate stages of the evolution have some differences. Each cosmological model contains two Type IV singularities which are chosen to occur one at the end of the inflationary era and one at the end of the matter domination era. The cosmological models at early times are approximately identical to the R 2 inflation model, so these describe a slow-roll inflationary era which ends when the slow-roll parameters become of order one. The inflationary era is followed by the radiation era and after that the matter domination era follows, which lasts until the second Type IV singularity, and then the late-time acceleration era follows. The models have two appealing features: firstly they produce a nearly scale invariant power spectrum of primordial curvature perturbations and a scalar-to-tensor ratio which are compatible with the most recent observational data and secondly, it seems that the deceleration-acceleration transition is crucially affected by the presence of the second Type IV singularity which occurs at the end of the matter domination era. As we demonstrate, the Hubble horizon at early times shrinks, as expected for an initially accelerating Universe, then during the matter domination era, it expands and finally after the Type IV singularity, the Hubble horizon starts to shrink again, during the late-time acceleration era. Intriguingly enough, the deceleration-acceleration transition, occurs after the second Type IV singularity. In addition, we investigate which F(R) gravity can successfully realize each of the four cosmological epochs.

Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

NASA Technical Reports Server (NTRS)

Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

2011-01-01

Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

Assessment of cell death mechanisms triggered by 177Lu-anti-CD20 in lymphoma cells.

PubMed

Azorín-Vega, E; Rojas-Calderón, E; Martínez-Ventura, B; Ramos-Bernal, J; Serrano-Espinoza, L; Jiménez-Mancilla, N; Ordaz-Rosado, D; Ferro-Flores, G

2018-08-01

The aim of this research was to evaluate the cell cycle redistribution and activation of early and late apoptotic pathways in lymphoma cells after treatment with 177 Lu-anti-CD20. Experimental and computer models were used to calculate the radiation absorbed dose to cancer cell nuclei. The computer model (Monte Carlo, PENELOPE) consisted of twenty spheres representing cells with an inner sphere (cell nucleus) embedded in culture media. Radiation emissions of the radiopharmaceutical located in cell membranes and in culture media were considered for nuclei dose calculations. Flow cytometric analyses demonstrated that doses as low as 4.8Gy are enough to induce cell cycle arrest and activate late apoptotic pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relation between acute and late irradiation impairment of four basic tastes and irradiated tongue volume in patients with head-and-neck cancer

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

Yamashita, Hideomi; Nakagawa, Keiichi; Nakamura, Naoki

2006-12-01

Purpose: Taste loss is a major cause of morbidity in patients undergoing head-and-neck irradiation. The relationship between the time course and the degree of taste disorder was studied in both acute and late phases. Methods and Materials: Taste ability was measured by the taste threshold for the four basic tastes using a filter paper disc method in patients before, during, and after radiotherapy. The subjects were divided into two groups. In Group A, Radiation fields included most of the tongue (n = 100), and in Group B Radiation fields did not include the tip of the tongue (n = 18).more » Results: In Group A, there was a significant impairment of the threshold of all four basic tastes at 3 weeks after starting radiotherapy (RT), and this impairment remained at 8 weeks (p < 0.05). This was not seen in Group B. In Group A, there was no significant difference in the patterns of taste sensitivity change between the high-dose (>20 Gy) and low-dose ({<=}20 Gy) groups. In the late phase, recovery of taste loss was seen in both groups since 4 months after completing RT. Conclusions: Unless the anterior part of the tongue was irradiated, taste loss was not observed during RT. When the anterior part of the tongue was irradiated, a difference by radiation dose was not observed in the taste loss pattern. Additionally, radiation-induced taste dysfunction appears to be a temporal effect.« less

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

Goda, Jayant Sastri; Le, Lisa W.; Lapperriere, Normand J.

Purpose: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients.more » Results: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade {>=}2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions: POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.« less

Chronic radiation-induced dermatitis: challenges and solutions.

PubMed

Spałek, Mateusz

2016-01-01

Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients' quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical trials are strongly needed to provide more efficacious therapies.

Polarized Continuum Radiation from Stellar Atmospheres

NASA Astrophysics Data System (ADS)

Harrington, J. Patrick

2015-10-01

Continuum scattering by free electrons can be significant in early type stars, while in late type stars Rayleigh scattering by hydrogen atoms or molecules may be important. Computer programs used to construct models of stellar atmospheres generally treat the scattering of the continuum radiation as isotropic and unpolarized, but this scattering has a dipole angular dependence and will produce polarization. We review an accurate method for evaluating the polarization and limb darkening of the radiation from model stellar atmospheres. We use this method to obtain results for: (i) Late type stars, based on the MARCS code models (Gustafsson et al. 2008), and (ii) Early type stars, based on the NLTE code TLUSTY (Lanz and Hubeny 2003). These results are tabulated at http://www.astro.umd.edu/~jph/Stellar_Polarization.html. While the net polarization vanishes for an unresolved spherical star, this symmetry is broken by rapid rotation or by the masking of part of the star by a binary companion or during the transit of an exoplanet. We give some numerical results for these last cases.

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

Chen, Shih-Yew; Napier, Bruce A.

The Program Area Committee 5 (PAC 5) of the National Council on Radiation protection and Measurements (NCRP) focuses its activities on environmental radiation and radioactive waste issues. The committee completed a number of reports in the subject areas, and specifically the most recent NCRP Report 175 (Decision Making for Late-Phase Recovery from Major Nuclear or Radiological Incidents). Historically PAC 5 addressed the emerging issues of the nation that pertain to radioactivity or radiation in the environment, or the radioactive waste issues due either to the natural origins or to the manmade activities

Advances in radiation oncology for the management of oropharyngeal tumors.

PubMed

Gunn, G Brandon; Frank, Steven J

2013-08-01

The major benefits of modern radiation therapy (eg, intensity-modulated [x-ray] radiation therapy [IMRT]) for oropharyngeal cancer are reduced xerostomia and better quality of life. Intensity-modulated proton therapy may provide additional advantages over IMRT by reducing radiation beam-path toxicities. Several acute and late treatment-related toxicities and symptom constellations must be kept in mind when designing and comparing future treatment strategies, particularly because currently most patients with oropharyngeal carcinoma present with human papillomavirus-positive disease and are expected to have a high probability of long-term survival after treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Neopterygian phylogeny: the merger assay

PubMed Central

Sferco, Emilia

2018-01-01

The phylogenetic relationships of the recently described genus †Ticinolepis from the Middle Triassic of the Monte San Giorgio are explored through cladistic analyses of the so far largest morphological dataset for fossil actinopterygians, including representatives of the crown-neopterygian clades Halecomorphi, Ginglymodi and Teleostei, and merging the characters from previously published systematic studies together with newly proposed characters. †Ticinolepis is retrieved as the most basal Ginglymodi and our results support the monophyly of Teleostei and Holostei, as well as Halecomorphi and Ginglymodi within the latter clade. The patterns of relationships within these clades mostly agree with those of previous studies, although a few important differences require future research. According to our results, ionoscopiforms are not monophyletic, caturids are not amiiforms and leptolepids and luisiellids form a monophyletic clade. Our phylogenetic hypothesis confirms the rapid radiation of the holostean clades Halecomorphi and Ginglymodi during the Early and Middle Triassic and the radiation of pholidophoriform teleosts during the Late Triassic. Crown-group Halecomorphi have an enormous ghost lineage throughout half of the Mesozoic, but ginglymodians and teleosts show a second radiation during the Early Jurassic. The crown-groups of Halecomorphi, Ginglymodi and Teleostei originated within parallel events of radiation during the Late Jurassic. PMID:29657820

Neopterygian phylogeny: the merger assay

NASA Astrophysics Data System (ADS)

López-Arbarello, Adriana; Sferco, Emilia

2018-03-01

The phylogenetic relationships of the recently described genus †Ticinolepis from the Middle Triassic of the Monte San Giorgio are explored through cladistic analyses of the so far largest morphological dataset for fossil actinopterygians, including representatives of the crown-neopterygian clades Halecomorphi, Ginglymodi and Teleostei, and merging the characters from previously published systematic studies together with newly proposed characters. †Ticinolepis is retrieved as the most basal Ginglymodi and our results support the monophyly of Teleostei and Holostei, as well as Halecomorphi and Ginglymodi within the latter clade. The patterns of relationships within these clades mostly agree with those of previous studies, although a few important differences require future research. According to our results, ionoscopiforms are not monophyletic, caturids are not amiiforms and leptolepids and luisiellids form a monophyletic clade. Our phylogenetic hypothesis confirms the rapid radiation of the holostean clades Halecomorphi and Ginglymodi during the Early and Middle Triassic and the radiation of pholidophoriform teleosts during the Late Triassic. Crown-group Halecomorphi have an enormous ghost lineage throughout half of the Mesozoic, but ginglymodians and teleosts show a second radiation during the Early Jurassic. The crown-groups of Halecomorphi, Ginglymodi and Teleostei originated within parallel events of radiation during the Late Jurassic.

Late skin damage in rabbits and monkeys after exposure to particulate radiations

NASA Technical Reports Server (NTRS)

Bergtold, D. S.; Cox, A. B.; Lett, J. T.; Su, C. M.

1983-01-01

Preliminary results are reported of experiments on the late effects of exposure to particulate radiations on stem cell populations. Skin biopsies were taken from the ears of rabbits irradiated 2-5 years previously with 530 MeV/amu Ar ions (LET 90 keV/micron), or 365 MeV/amu Ne ions (LET 35 keV micron), and from the chests and inner thighs of rhesus monkeys irradiated 16-18 years previously with 32-MeV protons (LET about 1.2 keV/micron). Skin fibroblast cultures obtained from the biopsy samples in rabbits were observed to undergo dose-dependent decreases in in vitro life span, with estimated survival curves showing the effects of Ar-ion irradiation to be more severe than those of Ne-ion irradiation. In addition, the healing of the biopsy wound was observed to become slower as radiation dose increased. In the monkey, radiation reduced the average number of fibroblasts at the time of cessation of growth in culture. Results thus demonstrate the capacity of skin sampling to reveal stem cell destruction, and have important implications for astronauts and other persons at risk of particle exposure with regard to healing responses to trauma or surgery.

Unappreciated diversification of stem archosaurs during the Middle Triassic predated the dominance of dinosaurs.

PubMed

Foth, Christian; Ezcurra, Martín D; Sookias, Roland B; Brusatte, Stephen L; Butler, Richard J

2016-09-15

Archosauromorpha originated in the middle-late Permian, radiated during the Triassic, and gave rise to the crown group Archosauria, a highly successful clade of reptiles in terrestrial ecosystems over the last 250 million years. However, scientific attention has mainly focused on the diversification of archosaurs, while their stem lineage (i.e. non-archosaurian archosauromorphs) has often been overlooked in discussions of the evolutionary success of Archosauria. Here, we analyse the cranial disparity of late Permian to Early Jurassic archosauromorphs and make comparisons between non-archosaurian archosauromorphs and archosaurs (including Pseudosuchia and Ornithodira) on the basis of two-dimensional geometric morphometrics. Our analysis recovers previously unappreciated high morphological disparity for non-archosaurian archosauromorphs, especially during the Middle Triassic, which abruptly declined during the early Late Triassic (Carnian). By contrast, cranial disparity of archosaurs increased from the Middle Triassic into the Late Triassic, declined during the end-Triassic extinction, but re-expanded towards the end of the Early Jurassic. Our study indicates that non-archosaurian archosauromorphs were highly diverse components of terrestrial ecosystems prior to the major radiation of archosaurs, including dinosaurs, while disparity patterns of the Ladinian and Carnian indicate a gradual faunal replacement of stem archosaurs by the crown group, including a short interval of partial overlap in morphospace during the Ladinian.

Are dark energy models with variable EoS parameter w compatible with the late inhomogeneous Universe?

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

Akarsu, Özgür; Bouhmadi-López, Mariam; Brilenkov, Maxim

We study the late-time evolution of the Universe where dark energy (DE) is presented by a barotropic fluid on top of cold dark matter (CDM) . We also take into account the radiation content of the Universe. Here by the late stage of the evolution we refer to the epoch where CDM is already clustered into inhomogeneously distributed discrete structures (galaxies, groups and clusters of galaxies). Under this condition the mechanical approach is an adequate tool to study the Universe deep inside the cell of uniformity. More precisely, we study scalar perturbations of the FLRW metric due to inhomogeneities ofmore » CDM as well as fluctuations of radiation and DE. For an arbitrary equation of state for DE we obtain a system of equations for the scalar perturbations within the mechanical approach. First, in the case of a constant DE equation of state parameter w, we demonstrate that our method singles out the cosmological constant as the only viable dark energy candidate. Then, we apply our approach to variable equation of state parameters in the form of three different linear parametrizations of w, e.g., the Chevallier-Polarski-Linder perfect fluid model. We conclude that all these models are incompatible with the theory of scalar perturbations in the late Universe.« less

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma

PubMed Central

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-01-01

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased (P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease (P = 0.022), and SD, 75th and 90th percentiles continued to increase (P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADCmean, ADCmin, kurtosis, and 25th, 50th, 75th, 90th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADCmax could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 (P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy. PMID:29050274

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma.

PubMed

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-19

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased ( P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease ( P = 0.022), and SD, 75 th and 90 th percentiles continued to increase ( P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADC mean , ADC min , kurtosis, and 25 th , 50 th , 75 th , 90 th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADC max could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 ( P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

Plio-Pleistocene climate sensitivity evaluated using high-resolution CO2 records.

PubMed

Martínez-Botí, M A; Foster, G L; Chalk, T B; Rohling, E J; Sexton, P F; Lunt, D J; Pancost, R D; Badger, M P S; Schmidt, D N

2015-02-05

Theory and climate modelling suggest that the sensitivity of Earth's climate to changes in radiative forcing could depend on the background climate. However, palaeoclimate data have thus far been insufficient to provide a conclusive test of this prediction. Here we present atmospheric carbon dioxide (CO2) reconstructions based on multi-site boron-isotope records from the late Pliocene epoch (3.3 to 2.3 million years ago). We find that Earth's climate sensitivity to CO2-based radiative forcing (Earth system sensitivity) was half as strong during the warm Pliocene as during the cold late Pleistocene epoch (0.8 to 0.01 million years ago). We attribute this difference to the radiative impacts of continental ice-volume changes (the ice-albedo feedback) during the late Pleistocene, because equilibrium climate sensitivity is identical for the two intervals when we account for such impacts using sea-level reconstructions. We conclude that, on a global scale, no unexpected climate feedbacks operated during the warm Pliocene, and that predictions of equilibrium climate sensitivity (excluding long-term ice-albedo feedbacks) for our Pliocene-like future (with CO2 levels up to maximum Pliocene levels of 450 parts per million) are well described by the currently accepted range of an increase of 1.5 K to 4.5 K per doubling of CO2.

Radiation-induced radioresistance of mammals and risk assessment

NASA Astrophysics Data System (ADS)

Smirnova, O.; Yonezawa, M.

It is shown experimentally that a preliminary low dose exposure can induce radioresistance in mice in two (early and late) periods after preirradiation. The manifestation of such effects is reduced mortality of pre-exposed specimens after challenge acute irradiation, the reason of the animal death being the hematopoietic subsyndrome of the acute radiation syndrome. Therefore, proceeding from the radiobiological concept of the critical system, the theoretical investigation of the influence of preirradiation on mammalian radiosensitivity is conducted by making use of mathematical models of the vital body system, hematopoiesis. Modeling results make it possible to elucidate the mechanisms of the radioprotection effect of low level priming irradiation on mammals. Specifically, the state of acquired radioresistance in mice is caused by reduced radiosensitivity of lymphopoietic and thrombocytopoietic systems in the early period and by reduced radiosensitivity of granulocytopoietic system in the late period after preirradiation. It is important to emphasize that the evaluations of the duration of the early and late periods of postirradiation radioresistance in mice, carried out on the basis of the modeling and experimental investigations, practically coincide. All this demonstrates the effectiveness of joint modeling and experimental methods in studies and predictions of modification effects of preirradiation on mammalian radiosensitivity. The results obtained show the importance of accounting such effects in radiation risk assessments for cosmonauts and astronauts on long-term missions.

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2016-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2015-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

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

Chang, David W., E-mail: David.Chang@petermac.org; Marvelde, Luc te; Chua, Boon H.

Purpose: To report the local recurrence rate and late toxicity of intraoperative radiation therapy (IORT) boost to the tumor bed using the Intrabeam System followed by external-beam whole-breast irradiation (WBI) in women with early-stage breast cancer in a prospective single-institution study. Methods and Materials: Women with breast cancer ≤3 cm were recruited between February 2003 and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface. This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patientsmore » were reviewed at regular, predefined intervals. Late toxicities were recorded using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring systems. Results: Fifty-five patients completed both IORT boost and external-beam WBI. Median follow-up was 3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous fibrosis was detected in 29 (53%) and 8 patients (15%), respectively. Conclusions: The use of IORT as a tumor bed boost using kV x-rays in breast-conserving therapy was associated with good local control but a clinically significant rate of grade 2 and 3 subcutaneous fibrosis.« less

Current advances in T-cell-based cancer immunotherapy

PubMed Central

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2015-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

Current advances in T-cell-based cancer immunotherapy.

PubMed

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2014-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

PubMed

Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

2016-11-01

The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

Radiobiological Impact of Reduced Margins and Treatment Technique for Prostate Cancer in Terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)

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

Jensen, Ingelise, E-mail: inje@rn.d; Carl, Jesper; Lund, Bente

2011-07-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on themore » Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications.« less

RADIATION THERAPY COMMUNICATION-REIRRADIATION OF A NASAL TUMOR IN A BRACHYCEPHALIC DOG USING INTENSITY MODULATED RADIATION THERAPY.

PubMed

Rancilio, Nicholas J; Custead, Michelle R; Poulson, Jean M

2016-09-01

A 5-year-old spayed female Shih Tzu was referred for evaluation of a nasal transitional carcinoma. A total lifetime dose of 117 Gy was delivered to the intranasal mass in three courses over nearly 2 years using fractionated intensity modulated radiation therapy (IMRT) to spare normal tissues. Clinically significant late normal tissue side effects were limited to bilaterally diminished tear production. The patient died of metastatic disease progression 694 days after completion of radiation therapy course 1. This case demonstrates that retreatment with radiation therapy to high lifetime doses for recurrent local disease may be well tolerated with IMRT. © 2016 American College of Veterinary Radiology.

Neotropics provide insights into the emergence of New World monkeys: New dental evidence from the late Oligocene of Peruvian Amazonia.

PubMed

Marivaux, Laurent; Adnet, Sylvain; Altamirano-Sierra, Ali J; Boivin, Myriam; Pujos, François; Ramdarshan, Anusha; Salas-Gismondi, Rodolfo; Tejada-Lara, Julia V; Antoine, Pierre-Olivier

2016-08-01

Recent field efforts in Peruvian Amazonia (Contamana area, Loreto Department) have resulted in the discovery of a late Oligocene (ca. 26.5 Ma; Chambira Formation) fossil primate-bearing locality (CTA-61). In this paper, we analyze the primate material consisting of two isolated upper molars, the peculiar morphology of which allows us to describe a new medium-sized platyrrhine monkey: Canaanimico amazonensis gen. et sp. nov. In addition to the recent discovery of Perupithecus ucayaliensis, a primitive anthropoid taxon of African affinities from the alleged latest Eocene Santa Rosa locality (Peruvian Amazonia), the discovery of Canaanimico adds to the evidence that primates were well-established in the Amazonian Basin during the Paleogene. Our phylogenetic results based on dental evidence show that none of the early Miocene Patagonian taxa (Homunculus, Carlocebus, Soriacebus, Mazzonicebus, Dolichocebus, Tremacebus, and Chilecebus), the late Oligocene Bolivian Branisella, or the Peruvian Canaanimico, is nested within a crown platyrrhine clade. All these early taxa are closely related and considered here as stem Platyrrhini. Canaanimico is nested within the Patagonian Soriacebinae, and closely related to Soriacebus, thereby extending back the soriacebine lineage to 26.5 Ma. Given the limited dental evidence, it is difficult to assess if Canaanimico was engaged in a form of pitheciine-like seed predation as is observed in Soriacebus and Mazzonicebus, but dental microwear patterns recorded on one upper molar indicate that Canaanimico was possibly a fruit and hard-object eater. If Panamacebus, a recently discovered stem cebine from the early Miocene of Panama, indicates that the crown platyrrhine radiation was already well underway by the earliest Miocene, Canaanimico indicates in turn that the "homunculid" radiation (as a part of the stem radiation) was well underway by the late Oligocene. These new data suggest that the stem radiation likely occurred in the Neotropics during the Oligocene, and that several stem lineages independently reached Patagonia during the early Miocene. Finally, we are still faced with a "layered" pattern of platyrrhine evolution, but modified in terms of timing of cladogeneses. If the crown platyrrhine radiation occurred in the Neotropics around the Oligocene-Miocene transition (or at least during the earliest Miocene), it was apparently concomitant with the diversification of the latest stem forms in Patagonia. Copyright © 2016 Elsevier Ltd. All rights reserved.

In search of radiation minima for balancing the needs of forest and water management in snow dominated watersheds (Invited)

NASA Astrophysics Data System (ADS)

Kumar, M.; Seyednasrollah, B.; Link, T. E.

2013-12-01

In upland snowfed forested watersheds, where the majority of melt recharge occurs, there is growing interest among water and forest managers to strike a balance between maximizing forest productivity and minimizing impacts on water resources. Implementation of forest management strategies that involve reduction of forest cover generally result in increased water yield and peak flows from forests, which has potentially detrimental consequences including increased erosion, stream destabilization, water shortages in late melt season, and degradation of water quality and ecosystem health. These ill effects can be partially negated by implementing optimal gap patterns and vegetation densities through forest management, that may minimize net radiation on snow-covered forest floor (NRSF). A small NRSF can moderate peak flows and increase water availability late in the melt season. Since forest canopies reduce direct solar (0.28 - 3.5 μm) radiation but increase longwave (3.5-100 μm) radiation at the snow surface, by performing detailed quantification of individual radiation components for a range of vegetation density and and gap configurations, we identify the optimal vegetation configurations. We also evaluate the role of site location, its topographic setting, local meteorological conditions and vegetation morphological characteristics, on the optimal configurations. The results can be used to assist forest managers to quantify the radiative regime alteration for various thinning and gap-creation scenarios, as a function of latitudinal, topographic, climatic and vegetation characteristics.

Soluble Dietary Fiber Ameliorates Radiation-Induced Intestinal Epithelial-to-Mesenchymal Transition and Fibrosis.

PubMed

Yang, Jianbo; Ding, Chao; Dai, Xujie; Lv, Tengfei; Xie, Tingbing; Zhang, Tenghui; Gao, Wen; Gong, Jianfeng; Zhu, Weiming; Li, Ning; Li, Jieshou

2017-11-01

Intestinal fibrosis is a late complication of pelvic radiotherapy. Epithelial-to-mesenchymal transition (EMT) plays an important role in tissue fibrosis. The aim of this study was to examine the effect of soluble dietary fiber on radiation-induced intestinal EMT and fibrosis in a mouse model. Apple pectin (4% wt/wt in drinking water) was administered to wild-type and pVillin-Cre-EGFP transgenic mice with intestinal fibrosis induced by a single dose of abdominal irradiation of 10 Gy. The effects of pectin on intestinal EMT and fibrosis, gut microbiota, and short-chain fatty acid (SCFA) concentration were evaluated. Intestinal fibrosis in late radiation enteropathy showed increased submucosal thickness and subepithelial collagen deposition. Enhanced green fluorescent protein (EGFP) + /vimentin + and EGFP + /α-smooth muscle actin (SMA) + coexpressing cells were most clearly observed at 2 weeks after irradiation and gradually decreased at 4 and 12 weeks. Pectin significantly attenuated the thickness of submucosa and collagen deposition at 12 weeks (24.3 vs 27.6 µm in the pectin + radiation-treated group compared with radiation-alone group, respectively, P < .05; 69.0% vs 57.1%, P < .001) and ameliorated EMT at 2 and 4 weeks. Pectin also modulated the intestinal microbiota composition and increased the luminal SCFA concentration. The soluble dietary fiber pectin protected the terminal ileum against radiation-induced fibrosis. This effect might be mediated by altered SCFA concentration in the intestinal lumen and reduced EMT in the ileal epithelium.

Infrared Photometric Study of Wolf–Rayet Galaxies

NASA Astrophysics Data System (ADS)

Chen, P. S.; Yang, X. H.; Liu, J. Y.; Shan, H. G.

2018-01-01

We collected observational data on 781 Wolf–Rayet (WR) galaxies from the literature to photometrically study their infrared properties measured by the 2MASS, WISE, IRAS, AKARI, and Herschel missions. It is found that in the 1–5 μm range the radiations of WR galaxies are dominated by the free–free emissions from the stellar winds and the circumstellar dust from the late-type stars in the host galaxy. In the 5–22 μm range, the radiation of WR galaxies is dominated by the free–free emissions and the synchrotron radiation from the central active galactic nucleus (AGN; but not always present). In the 22–140 μm range, the radiations of WR galaxies are dominated by the free–free emissions and the star formation/starburst activities. In the 250–500 μm range, the radiation of WR galaxies is dominated by the free–free emissions. In addition, the comparison with the non-WR galaxies is made. It is shown that some star formation WR galaxies have redder near-infrared colors than non-WR star-forming galaxies probably due to the gas emission in the near-infrared. In the 2–5 μm region WR galaxies have redder colors due to the thermal emission from circumstellar dust of late-type stars and the enhanced gas emission. In the 5–22 μm region, both WR galaxies and non-WR galaxies have similar behavior, indicative of having similar free–free emission as the dominant radiation. In the 25–140 μm region, both types of galaxies also have similar behavior, indicative of having free–free emission from the stellar winds or the thermal radiation from the starburst/star formation as the dominant radiation.

Assessing the Impact of Air Pollution on Grain Yield of Winter Wheat - A Case Study in the North China Plain.

PubMed

Liu, Xiuwei; Sun, Hongyong; Feike, Til; Zhang, Xiying; Shao, Liwei; Chen, Suying

2016-01-01

The major wheat production region of China the North China Plain (NCP) is seriously affected by air pollution. In this study, yield of winter wheat (Triticum aestivum L.) was analyzed with respect to the potential impact of air pollution index under conditions of optimal crop management in the NCP from 2001 to 2012. Results showed that air pollution was especially serious at the early phase of winter wheat growth significantly influencing various weather factors. However, no significant correlations were found between final grain yield and the weather factors during the early growth phase. In contrast, significant correlations were found between grain yield and total solar radiation gap, sunshine hour gap, diurnal temperature range and relative humidity during the late growing phase. To disentangle the confounding effects of various weather factors, and test the isolated effect of air pollution induced changes in incoming global solar radiation on yield under ceteris paribus conditions, crop model based scenario-analysis was conducted. The simulation results of the calibrated Agricultural Production Systems Simulator (APSIM) model indicated that a reduction in radiation by 10% might cause a yield reduction by more than 10%. Increasing incident radiation by 10% would lead to yield increases of (only) 7%, with the effects being much stronger during the late growing phase compared to the early growing phase. However, there is evidence that APSIM overestimates the effect of air pollution induced changes on radiation, as it does not consider the changes in radiative properties of solar insulation, i.e. the relative increase of diffuse over direct radiation, which may partly alleviate the negative effects of reduced total radiation by air pollution. Concluding, the present study could not detect a significantly negative effect of air pollution on wheat yields in the NCP.

Biomarkers Indigenous to Late Archean Rocks

NASA Astrophysics Data System (ADS)

Eigenbrode, J. L.; Freeman, K. H.; Summons, R. E.; Love, G. D.; Snape, C. E.

2003-12-01

Two new lines of evidence support the authenticity of molecular fossils in late Archean rocks of the Hamersley Province, Western Australia. Specifically, they support 1) a syngenetic relationship between the kerogen and extractable biomarkers, and 2) a indigenous relationship between extractable compounds and the host rocks. Carbon skeletons released from kerogen via high-pressure hydropyrolysis match those found in associated extracted bitumen. Biomarker ratios indicate less mature steranes and terpanes (i.e. hopanes and tricyclic terpanes) are embedded in the kerogen matrix as compared to the highly mature steranes and terpanes in the extracts, which is similar to findings in other hydropyrolysis experiments. Lithology-associated variations in biomarker distributions are noteworthy and suggest environmental settings are associated with differing biotic ecosystems. The evidence reported here confirms the 2.7 Ga antiquity of diverse biosynthetic pathways. Molecular data, together with isotopic data, indicate aerobic and anaerobic respiration pathways were fundamental to the complex microbial biogeochemistry of the late Archean. The biomarkers in these rocks support an early radiation of the three domains of life and radiation within the bacteria, such that clades of cyanobacteria, green sulfur bacteria, and proteobacteria had been established.

[Effects of radiation exposure on human body].

PubMed

Kamiya, Kenji; Sasatani, Megumi

2012-03-01

There are two types of radiation health effect; acute disorder and late on-set disorder. Acute disorder is a deterministic effect that the symptoms appear by exposure above a threshold. Tissues and cells that compose the human body have different radiation sensitivity respectively, and the symptoms appear in order, from highly radiosensitive tissues. The clinical symptoms of acute disorder begin with a decrease in lymphocytes, and then the symptoms appear such as alopecia, skin erythema, hematopoietic damage, gastrointestinal damage, central nervous system damage with increasing radiation dose. Regarding the late on-set disorder, a predominant health effect is the cancer among the symptoms of such as cancer, non-cancer disease and genetic effect. Cancer and genetic effect are recognized as stochastic effects without the threshold. When radiation dose is equal to or more than 100 mSv, it is observed that the cancer risk by radiation exposure increases linearly with an increase in dose. On the other hand, the risk of developing cancer through low-dose radiation exposure, less 100 mSv, has not yet been clarified scientifically. Although uncertainty still remains regarding low level risk estimation, ICRP propound LNT model and conduct radiation protection in accordance with LNT model in the low-dose and low-dose rate radiation from a position of radiation protection. Meanwhile, the mechanism of radiation damage has been gradually clarified. The initial event of radiation-induced diseases is thought to be the damage to genome such as radiation-induced DNA double-strand breaks. Recently, it is clarified that our cells could recognize genome damage and induce the diverse cell response to maintain genome integrity. This phenomenon is called DNA damage response which induces the cell cycle arrest, DNA repair, apoptosis, cell senescence and so on. These responses act in the direction to maintain genome integrity against genome damage, however, the death of large number of cells results in acute disorder, and then DNA mis-repair and mutation is speculated to cause cancer. The extent to which this kind of cellular response could reduce the low-dose radiation risk is a major challenge for future research.

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

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

Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority givenmore » to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study may help to stratify patients at risk for late effects to develop strategies to reduce frequency and severity of radiation sequelae.« less

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

PubMed

Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

2012-01-01

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study may help to stratify patients at risk for late effects to develop strategies to reduce frequency and severity of radiation sequelae. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Late Toxicity and Patient Self-Assessment of Breast Appearance/Satisfaction on RTOG 0319: A Phase 2 Trial of 3-Dimensional Conformal Radiation Therapy-Accelerated Partial Breast Irradiation Following Lumpectomy for Stages I and II Breast Cancer

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

Chafe, Susan, E-mail: susan.chafe@albertahealthservices.ca; Moughan, Jennifer; McCormick, Beryl

2013-08-01

Purpose: Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Methods and Materials: Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adversemore » Events, version 3.0, was used to grade toxicity. Results: Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Conclusions: Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again.« less

Late toxicity and patient self-assessment of breast appearance/satisfaction on RTOG 0319: a phase 2 trial of 3-dimensional conformal radiation therapy-accelerated partial breast irradiation following lumpectomy for stages I and II breast cancer.

PubMed

Chafe, Susan; Moughan, Jennifer; McCormick, Beryl; Wong, John; Pass, Helen; Rabinovitch, Rachel; Arthur, Douglas W; Petersen, Ivy; White, Julia; Vicini, Frank A

2013-08-01

Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to grade toxicity. Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again. Copyright © 2013. Published by Elsevier Inc.

Evaluation of acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary.

PubMed

Yildirim, G; Ozsaran, Z; Yalman, D; Kamer, S; Aras, A

2008-01-01

The purpose of this study was to evaluate acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary, and to compare the usefulness and disadvantages of each system. Between February 2001 and February 2003, 107 patients with gynaecologic malignancy who received either radical or djuvant external radiotherapy +/- intracavitary brachytherapy or radiochemotherapy were enrolled in this study. The patients were evaluated before radiotherapy and weekly during radiotherapy for acute morbidity using the RTOG grading system and Franco-Italian glossary. Postradiotherapy evaluation was done one month after radiotherapy and at 3-month intervals thereafter. Median follow-up duration was 17 months. Morbidity was graded and recorded according to each scoring system. Median age was 46 years (range 37-82). Sixty-four patients (59.8%) had endometrial cancer. Radical radiotherapy was applied to 26 patients because of inoperability and 81 patients received postoperative radiotherapy. Biologically effective doses for the bladder, rectum and vagina were 98.39, 103.54 and 121.81, respectively, for late morbidity (BED3); 70.88, 72.84 and 80.92, respectively, for acute morbidity (BED10). According to the RTOG grading system acute morbidity rate for the genitourinary and gastrointestinal systems, and skin were 52.3%, 83.2% and 63.5%, respectively. Late morbidity rate for the bladder, colon-rectum, skin and vagina were 16.8%, 20.6%, 47.7% and 51.4%, respectively. The morbidity rate for the bladder, nonspecific abdominal, hematopoietic system, uterus-vulva-vagina, skin and rectum were 35.4%, 29.9%, 5.6%, 60.8%, 40.1% and 32.7%, respectively using the Franco-Italian glossary. In patients with carcinoma of the vulva--whose treatment fields were wider--acute morbidity rate according to RTOG criteria was higher (p = 0.057); photon energy (6 Mv rather than 1.25 MV) (p = 0.01) and treatment interruption of more than eight days (p = 0.019) were correlated with decreased long-term morbidity. According to the Franco-Italian glossary morbidity rates were higher in patients who received chemotherapy (p = 0.047), both external radiotherapy and brachytherapy (p = 0.022) and treatment interruption of less than eight days (p = 0.019). There is no common language between the RTOG grading system and Franco-Italian glossary for defining and scoring radiation morbidity. Up to date no standard and well-defined system has been developed for recording and reporting acute and late radiation morbidity in gynaecologic malignancy, but rather it depends on the subjective evaluation and experience of a radiation oncologist and subjective complaints of the patient, and sometimes on clinical findings. A standard and well-defined user friendly objective scoring system is needed to define and predict the morbidity rate more properly.

Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies

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

Salama, Joseph K.; Mundt, Arno J.; Department of Radiation Oncology, University of Illinois, Chicago, IL

2006-07-15

Purpose: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. Methods and Materials: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aorticmore » lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. Results: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. Conclusions: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.« less

Variation in Telangiectasia Predisposing Genes Is Associated With Overall Radiation Toxicity

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

Tanteles, George A.; Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester; Murray, Robert J.S.

2012-11-15

Purpose: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. Methods and Materials: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were withinmore » the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. Results: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. Conclusions: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects.« less

Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

PubMed

Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

2017-12-01

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

Early cosmology constrained

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

Verde, Licia; Jimenez, Raul; Bellini, Emilio

We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter Ω{sub MR} < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < N {sub eff} < 3.2 when imposing flatness. Our constraintsmore » thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is r {sub s} = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to r {sub s} = 150 ± 5 Mpc.« less

Early cosmology constrained

NASA Astrophysics Data System (ADS)

Verde, Licia; Bellini, Emilio; Pigozzo, Cassio; Heavens, Alan F.; Jimenez, Raul

2017-04-01

We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter ΩMR < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < Neff < 3.2 when imposing flatness. Our constraints thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is rs = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to rs = 150 ± 5 Mpc.

Analytical Solution of the Radiative Transfer Equation in a Thin Dusty Circumstellar Shell

NASA Astrophysics Data System (ADS)

Cruzalèbes, P.; Sacuto, S.

The radiative transfer equation can be solved analytically for optically thin shells. The solution leads to a semi-analytical expression of the visibility function, which can be compared to the numerical solution given by the DUSTY code. Best-fit model parameters are given using real measurements of ISO fluxes, ISI and VLTI-MIDI visibilities for 3 late-type stars.

Gamma radiation tolerance in different life stages of the fruit fly Drosophila melanogaster.

PubMed

Paithankar, Jagdish Gopal; Deeksha, K; Patil, Rajashekhar K

2017-04-01

Insects are known to have higher levels of radiation tolerance than mammals. The fruit fly Drosophila provides opportunities for genetic analysis of radiation tolerance in insects. A knowledge of stage-specific sensitivity is required to understand the mechanisms and test the existing hypothesis of insect radiation tolerance. Drosophila melanogaster were irradiated using gamma rays at different life stages. Irradiation doses were chosen to start from 100-2200 Gy with increments of 100 Gy, with a dose rate of 12.5 and 25 Gy/min. The threshold of mortality, LD 50 and LD 100 1 h post-irradiation was recorded for larvae and adults and 24 h post-irradiation for eggs and after 2-3 days for early and late pupae. Total antioxidant capacity for all the life stages was measured using the phosphomolybdenum method. Twenty-four hours post-irradiation, 100% mortality was recorded for eggs at 1000 Gy. One hour post irradiation 100% mortality was recorded at 1300 Gy for first instar larvae, 1700 Gy for second instar larvae, 1900 Gy for feeding third instar larvae and 2200 Gy for non-feeding third instar larvae. Post-irradiation complete failure of emergence (100% mortality) was observed at 130 Gy for early pupae and 1500 Gy for late pupae; 100% mortality was observed at 1500 Gy for adults. The values of LD 50 were recorded as 452 Gy for eggs, 1049 Gy for first instar larvae, 1350 Gy for second instar larvae, 1265 Gy for feeding third instar larvae, 1590 Gy for non-feeding third instar larvae, 50 Gy for early pupae, 969 Gy for late pupae, 1228 Gy for adult males and 1250 Gy for adult females. Early pupae were found to be prone to radiation, whereas the non-feeding third instar larvae were most resistant among all stages. The chromosome number being constant and total antioxidant capacity being nearly constant in all stages, we suggest that high rate of cell division during early pupae makes this stage sensitive to radiation.

The Impact of Combined Radiation and Chemotherapy on Outcome in Uterine Clear Cell Carcinoma Compared with Chemotherapy Alone.

PubMed

Mahdi, H; Moulton, L; Nutter, B; Cherian, S; Rose, P

2016-12-01

To investigate the impact of pelvic radiation on survival in patients with uterine clear cell carcinoma (UCC) who received adjuvant chemotherapy. Patients with stage I-IV UCC who had undergone surgery and chemotherapy were identified from the Surveillance, Epidemiology, and End Results (SEER) programm 2000-2009. Patients were divided into those who received only chemotherapy and those who received both chemotherapy and radiation therapy. Kaplan-Meier curves and Cox regression models were used for analysis. Of the 317 patients included, 195 (62%) were in the chemotherapy only group and 122 (38%) were in the chemotherapy and radiation therapy group. Pelvic radiation was associated with significant improvement in overall survival (median 88 versus 25 months, 5 year survival: 58% versus 33%, P<0.001) in the chemotherapy and radiation therapy group compared with the chemotherapy only group for the entire cohort. On subset analysis, chemotherapy and radiation therapy was associated with improved overall survival in late stage disease (III-IV) (5 year 54% versus 22%, P<0.001) compared with the chemotherapy only group, whereas in stage I-II UCC, there was no difference in overall survival between the chemotherapy and radiotherapy group and the chemotherapy only group (5 year 65% versus 67%, P=0.69). In multivariable analysis, pelvic radiation was associated with improved survival in patients with late stage disease (hazard ratio 0.57, 95% confidence interval 0.35-0.94, P=0.03) but not for early stage disease (hazard ratio 0.81, 95% confidence interval 0.33-2.0, P=0.65). Other significant predictors were advanced stage, positive cytology and extensive lymphadenectomy. Radiation was associated with significant improvement in survival in advanced stage UCC, but not in early stage UCC. These data support the beneficial role of radiation therapy in UCC, especially in patients with advanced stage disease. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A Review: Some biological effects of high LET radiations

NASA Technical Reports Server (NTRS)

Wiley, A., Jr.

1972-01-01

There are qualitative and quantitative differences in the biological damage observed after exposure to high LET radiation as compared to that caused by low LET radiations. This review is concerned with these differences, which are ultimately reflected at the biochemical, cellular and even whole animal levels. In general, high LET radiations seem to produce biochemical damage which is more severe and possibly less repairable. Experimental data for those effects are presented in terms of biochemical RBE's with consideration of both early and late manifestations. An LET independent process by which significant biochemical damage may result from protons, neutrons and negative pion mesons is discussed.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

PubMed

Tougeron, David; Savoye, Guillaume; Savoye-Collet, Céline; Koning, Edith; Michot, Francis; Lerebours, Eric

2009-08-01

Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

PubMed

Pallawela, S N S; Sullivan, A K; Macdonald, N; French, P; White, J; Dean, G; Smith, A; Winter, A J; Mandalia, S; Alexander, S; Ison, C; Ward, H

2014-06-01

Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Medical therapy of inflammatory bowel diseases: ulcerative colitis].

PubMed

Lakatos, László; Lakatos, Péter László

2007-06-24

There are fewer significant changes in the medical therapy of ulcerative colitis (UC) compared to Crohn's disease. The most important factors that determine therapy are disease extent and severity. 5-aminosalicylates (5-ASA) constitute the treatment of choice in mild-to-moderate UC. The efficacy of new compounds (e.g. mesalazine) is only mildly improved compared to sulphasalazine; however, their use has become more frequent due to a more favorable side effects profile. Topical medication is more effective in proctitis and distal colitis, and the combination of topical and orally-administered drugs is superior to oral therapy alone also in extensive disease. Thus, this latter regimen should be considered for cases where the escalation of treatment is required. Systemic steroids still represent the first line therapy in acute, severe UC, while in patients who do not respond to steroids, cyclosporine and infliximab should be considered as a second line therapy and as alternatives for colectomy. Maintenance treatment is indicated in all UC cases. 5-ASA compounds are suggested as first line maintenance therapy with the optimal dose still being under investigation. Topical compounds are effective also for maintenance in distal colitis or proctitis, if accepted by the patients. Immunosuppressives, especially azathioprine, should be considered in chronically active, steroid dependent or resistant patients. According to recent publications, azathioprine is almost equally effective in UC and CD. The question of chemoprevention is important during maintenance. There are increasing data supporting the notion that aminosalicylates may lower the risk for UC-associated colorectal cancer. The most important changes in the management of UC are the more frequent use of topical aminosalicylates and azathioprine, the availability of infliximab in severe UC, and increasing use of aminosalicylates for chemoprevention of colorectal carcinoma. Furthermore, adequate attention is needed to better organize the patient-doctor relationship and for greater adherence to medical therapy.

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Sasaki, Hidetaka; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group.

PubMed

Yoshioka, Yasuo; Suzuki, Osamu; Nishimura, Kazuo; Inoue, Hitoshi; Hara, Tsuneo; Yoshida, Ken; Imai, Atsushi; Tsujimura, Akira; Nonomura, Norio; Ogawa, Kazuhiko

2013-01-01

We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0-11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right-left, superior-inferior, and anterior-posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2-3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding.

Predatory Dinosaurs from the Sahara and Late Cretaceous Faunal Differentiation

PubMed

Sereno; Dutheil; Iarochene; Larsson; Lyon; Magwene; Sidor; Varricchio; Wilson

1996-05-17

Late Cretaceous (Cenomanian) fossils discovered in the Kem Kem region of Morocco include large predatory dinosaurs that inhabited Africa as it drifted into geographic isolation. One, represented by a skull approximately 1.6 meters in length, is an advanced allosauroid referable to the African genus Carcharodontosaurus. Another, represented by a partial skeleton with slender proportions, is a new basal coelurosaur closely resembling the Egyptian genus Bahariasaurus. Comparisons with Cretaceous theropods from other continents reveal a previously unrecognized global radiation of carcharodontosaurid predators. Substantial geographic differentiation of dinosaurian faunas in response to continental drift appears to have arisen abruptly at the beginning of the Late Cretaceous.

Computational Model of the Modulation of Gene Expression Following DNA Damage

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Dicello, J. F.; Nikjoo, H.; Cherubini, R.

2002-01-01

High linear energy transfer (LET) radiation, such as heavy ions or neutrons, has an increased biological effectiveness compared to X rays for gene mutation, genomic instability, and carcinogenesis. In the traditional paradigm, mutations or chromosomal aberrations are causative of late effects. However, in recent years experimental evidence has demonstrated the important role of the description of the modification of gene expression by radiation in understanding the mechanisms of radiation action. In this report, approaches are discussed to the mathematical description of mRNA and protein expression kinetics following DNA damage. Several hypotheses for models of radiation modulation of protein expression are discussed including possible non-linear processes that evolve from the linear dose responses that follow the initial DNA damage produced by radiation.

Scalar perturbations in the late Universe: viability of the Chaplygin gas models

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

Bouhmadi-López, Mariam; Brilenkov, Maxim; Brilenkov, Ruslan

We study the late-time evolution of the Universe where dark energy (DE) is parametrised by a modified generalised Chaplygin gas (mGCG) on top of cold dark matter (CDM) . We also take into account the radiation content of the Universe. In this context, the late stage of the evolution of the universe refers to the epoch where CDM is already clustered into inhomogeneously distributed discrete structures (galaxies, groups and clusters of galaxies). Under these conditions, the mechanical approach is an adequate tool to study the Universe deep inside the cell of uniformity. To be more accurate, we study scalar perturbationsmore » of the Friedmann-Lemaȋtre-Robertson-Walker metric due to inhomogeneities of CDM as well as fluctuations of radiation and mGCG, the later driving the late-time acceleration of the universe. Our analysis applies as well to the case where mGCG plays the role of DM and DE . We select the sets of parameters of the mGCG that are compatible with the mechanical approach. These sets define prospective mGCG models. By comparing the selected sets of models with some of the latest observational data results, we conclude that the mGCG is in tight agreement with those observations particularly for a mGCG playing the role of DE and DM.« less

Icezones instead of firewalls: extended entanglement beyond the event horizon and unitary evaporation of a black hole

NASA Astrophysics Data System (ADS)

Hutchinson, John; Stojkovic, Dejan

2016-07-01

We examine the basic assumptions in the original setup of the firewall paradox. The main claim is that a single mode of the lathe radiation is maximally entangled with the mode inside the horizon and simultaneously with the modes of early Hawking radiation. We argue that this situation never happens during the evolution of a black hole. Quantum mechanics tells us that while the black hole exists, unitary evolution maximally entangles a late mode located just outside the horizon with a combination of early radiation and black hole states, instead of either of them separately. One of the reasons for this is that the black hole radiation is not random and strongly depends on the geometry and charge of the black hole, as detailed numerical calculations of Hawking evaporation clearly show. As a consequence, one can not factor out the state of the black hole. However, this extended entanglement between the black hole and modes of early and late radiation indicates that, as the black hole ages, the local Rindler horizon is modified out to macroscopic distances from the black hole. Fundamentally non-local physics nor firewalls are not necessary to explain this result. We propose an infrared mechanism called icezone that is mediated by low energy interacting modes and acts near any event horizon to entangle states separated by long distances. These interactions at first provide small corrections to the thermal Hawking radiation. At the end of evaporation however the effect of interactions is as large as the Hawking radiation and information is recovered for an outside observer. We verify this in an explicit construction and calculation of the density matrix of a spin model.

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status.

PubMed

Singh, Vijay K; Garcia, Melissa; Seed, Thomas M

2017-09-01

The threat of a radiological/nuclear event is a critical concern for all government agencies involved in national security and public health preparedness. Countermeasures that are safe, easily administered, and effective at diminishing or eliminating adverse health effects to individuals and the overall public health impact of radiation exposure are urgently needed. Radiation countermeasures included in this three-part series have been classified under various subheadings based specifically on their developmental stages for United States Food and Drug Administration (FDA) approval. We have included FDA-approved agents for acute radiation syndrome (ARS) in part I. This is part II in which we have reviewed FDA-approved agents for limited indications, internalized radionuclides, emesis, late effects, radiomitigators available in the strategic national stockpile (SNS), agents with FDA investigational new drug (IND) status, and those with NHP efficacy data without FDA IND. Agents discussed in part III are those agents that have been peer reviewed, published, and have demonstrated significant survival benefits in animal models of ARS. Agents investigated in in vitro models only or studied in animal models without peer-reviewed publications have not been included. The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. A number of promising radiation countermeasures are currently moving forward with continued support and effort by both governmental agencies and by publicly and privately held pharmaceutical companies. There is a limited number of countermeasures which are progressing well following the Animal Rule and may get approved in the near future, thus serving to close the gap of this critically important, unmet radiobiomedical need.

Treatment Option Overview (Ewing Sarcoma)

MedlinePlus

... for Ewing sarcoma have an increased risk of acute myeloid leukemia and myelodysplastic syndrome . There is also an increased risk of sarcoma in the area treated with radiation therapy . Some late effects may be treated or ...

Stages of Ewing Sarcoma

MedlinePlus

... for Ewing sarcoma have an increased risk of acute myeloid leukemia and myelodysplastic syndrome . There is also an increased risk of sarcoma in the area treated with radiation therapy . Some late effects may be treated or ...

Massive osteolysis of the right clavicle developing after radiation therapy

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

Skinner, W.L.; Buzdar, A.U.; Libshitz, H.I.

1988-07-15

This report describes an unusual case of clavicular osteolysis, a late complication of radiation therapy for breast cancer, and demonstrates the diagnostic implications that radiotherapy changes can pose. Radiotherapy to the chest wall produces a spectrum of alterations in bone over time, ranging from early roentgenographic findings of osteoporosis and trabecular thickening to spontaneous fractures and changes that may be confused with metastatic disease or postirradiation sarcoma.

IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

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

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; Madani, Indira; Morbee, Lieve

2012-05-01

Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages weremore » T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival. Avoidance of severe dry eye syndrome and radiation-induced blindness suggests IMRT as a standard treatment for sinonasal tumors.« less

Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens.

PubMed

Tandberg, Daniel J; Oyekunle, Taofik; Lee, W Robert; Wu, Yuan; Salama, Joseph K; Koontz, Bridget F

2018-06-01

To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT). Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up. Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059). HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute toxicity and its dosimetric correlates for high-risk prostate cancer treated with moderately hypofractionated radiotherapy

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

Arunsingh, Moses; Mallick, Indranil, E-mail: imallick@gmail.com; Prasath, Sriram

Aims: To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer. Methods: A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65 Gy/25 Fr/5 weeks (n = 18), or 60 Gy/20 Fr/4 weeks (n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified. Results: The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2more » genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2 Gy equivalent doses (EQD2) to the rectum and bladder (α/β = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V{sub EQD2-60} {sub Gy} (13.2 vs 9.9 cc, p = 0.007) and V{sub EQD2-50} {sub Gy} (20.6 vs 15.4 cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher V{sub EQD2-70} {sub Gy} (30.4 vs 18.4 cc, p = 0.001) and V{sub EQD2-65} {sub Gy} (44.0 vs 28.8 cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for V{sub EQD2-60} {sub Gy} was 9.7 cc and for V{sub EQD2-50} {sub Gy} was 15.9 cc. For grade 2 GU symptoms, the threshold values were 23.6 cc for V{sub EQD2-70} {sub Gy} and 38.1 cc for V{sub EQD2-65} {sub Gy}. Conclusions: Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.« less

Alaskan Ice Core Shows Relationship Between Asian Dust Storm And The Stratosphere Troposphere Exchange

NASA Astrophysics Data System (ADS)

Yasunari, T. J.; Shiraiwa, T.; Kanamori, S.; Fujii, Y.; Igarashi, M.; Yamazaki, K.; Benson, C. S.; Hondoh, T.

2005-12-01

Atmospheric dust absorbs and scatters solar radiation, and affects global radiative balance. Dust storm in arid and semi-arid regions in East Asia is main dust source in the northern hemisphere. Asian dust has large effect on radiative balance in the northern hemisphere and its long range transport to Alaskan region frequently occurs in springtime. On the other hand, the stratosphere-troposphere exchange (STE) is a important phenomenon for material exchange among the spheres. Some parameters such as tritium, ozone and beryllium can be transferred from the stratosphere into the troposphere under some conditions such as tropopause folding outbreaks, cut-off low developing and cyclonic activities. STE has a seasonal exchange with maximum in springtime. In June 2003, a 50m ice core was drilled at the summit of Mount Wrangell volcano (60N, 144W, 4100 m), Alaska. Dust particle concentration, tritium content and ratio of stable hydrogen isotope were analyzed. Tritium is the stratospheric tracer recently because the effect of nuclear tests in 1960s has faded these days, and its concentration is highest north of 30th parallel. Therefore, the ice core drilled here is ideal to assess both the Asian dust transport and STE. The core covers 1992-2002 with divided four seasons (winter, spring, late-spring and summer). Fine dust less than one micro meter generally represents long range transport increased in springtime every year. The drastic fine and coarse dust flux increases after 2000 correspond to recent increase of Asian Dust outbreaks. These indicate that Asian dust storm largely affects Mount Wrangell every year. Here we show the fact that highest positive correlation between tritium and fine dust fluxes was seen in the term from late-spring to summer (also high correlation between tritium and coarse dust fluxes in this term), suggesting that the stratosphere-troposphere exchange was most intensified by Asian dust storms in this transient season from spring to summer. Asian dust and STE are dominant in springtime. However, our results showed that these activities related each other the most from late-spring to summer. Asian dust storm and STE are not active in summer. Hence, our results are assumed to mainly reflect late-spring relationship between Asian dust storm and STE. Asian dust outbreaks with severe weather would impact on vertical and horizontal material circulation from the stratosphere to the troposphere. Further studies for Asian dust and STE especially focused on late-spring may lead to elucidate the mechanism of material circulation and assess the radiative forcing of Asian dust in springtime.

Fistulizing Crohn's disease: Diagnosis and management.

PubMed

Gecse, Krisztina; Khanna, Reena; Stoker, Jaap; Jenkins, John T; Gabe, Simon; Hahnloser, Dieter; D'Haens, Geert

2013-06-01

Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.

Asymptomatic urethral lymphogranuloma venereum: a case report.

PubMed

Charest, Louise; Fafard, Judith; Greenwald, Zoë R

2018-07-01

Since 2003, there has been a resurgence of lymphogranuloma venereum (LGV), a variant of Chlamydia trachomatis (CT), among men who have sex with men (MSM) in several urban areas of Europe and North America. LGV infection occurs most often at anal sites causing proctitis. Urethral and oropharyngeal infections are rare. In Quebec, LGV incidence has been increasing exponentially in recent years and the current guidelines support systematic LGV genotype testing among anorectal CT-positive samples only. This case report describes a patient with a urethral LGV infection, remarkable due to its prolonged asymptomatic development prior to the manifestation of an inguinal bubo. Physicians should be vigilant of potential cases of LGV and forward CT-positive samples occurring among individuals with LGV risk factors for genotype testing.

Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

PubMed Central

Corre, Isabelle; Guillonneau, Maëva; Paris, François

2013-01-01

Tumor areas can now be very precisely delimited thanks to technical progress in imaging and ballistics. This has also led to the development of novel radiotherapy protocols, delivering higher doses of ionizing radiation directly to cancer cells. Despite this, radiation toxicity in healthy tissue remains a major issue, particularly with dose-escalation in these new protocols. Acute and late tissue damage following irradiation have both been linked to the endothelium irrigating normal tissues. The molecular mechanisms involved in the endothelial response to high doses of radiation are associated with signaling from the plasma membrane, mainly via the acid sphingomyelinase/ceramide pathway. This review describes this signaling pathway and discusses the relevance of targeting endothelial signaling to protect healthy tissues from the deleterious effects of high doses of radiation. PMID:24252908

Effects of Ionizing Radiation on the Heart

PubMed Central

Boerma, Marjan; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Nelson, Gregory A.; Cheema, Amrita K.; Koturbash, Igor; Singh, Sharda P.; Tackett, Alan J.; Hauer-Jensen, Martin

2016-01-01

This article provides an overview of studies addressing effects of ionizing radiation on the heart. Clinical studies have identified early and late manifestations of radiation-induced heart disease, a side effect of radiation therapy to tumors in the chest when all or part of the heart is situated in the radiation field. Studies in preclinical animal models have contributed to our understanding of the mechanisms by which radiation may injure the heart. More recent observations in human subjects suggest that ionizing radiation may have cardiovascular effects at lower doses than was previously thought. This has led to examinations of low-dose photons and low-dose charged particle irradiation in animal models. Lastly, studies have started to identify noninvasive methods for detection of cardiac radiation injury and interventions that may prevent or mitigate these adverse effects. Altogether, this ongoing research should increase our knowledge of biological mechanisms of cardiovascular radiation injury, identify non-invasive biomarkers for early detection, and potential interventions that may prevent or mitigate these adverse effects. PMID:27919338

How sensitive is Hawking radiation to superluminal dispersion relations?

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

Jannes, G.; Instituto de Estructura de la Materia, CSIC, Serrano 121, 28006 Madrid; Barcelo, C.

2009-05-01

We discuss the Hawking radiation process in a collapse scenario with superluminal dispersion relations. Due to these superluminal modifications, the horizon effectively becomes frequency-dependent. At every moment of the collapse, a critical frequency can be calculated such that frequencies higher than this critical frequency do not couple to the collapsing geometry and hence do not see any horizon. We discuss three important consequences. First, the late-time radiation in general has a lower intensity than in the standard Hawking picture. Second, the thermal output spectrum depends on the surface gravity, thereby effectively exploring the physics inside the black hole. Third, themore » radiation dies off as time advances.« less

On the late-time cosmology of a condensed scalar field

NASA Astrophysics Data System (ADS)

Ghalee, Amir

2016-04-01

We study the late-time cosmology of a scalar field with a kinetic term non-minimally coupled to gravity. It is demonstrated that the scalar field dominate the radiation matter and the cold dark matter (CDM). Moreover, we show that eventually the scalar field will be condensed and results in an accelerated expansion. The metric perturbations around the condensed phase of the scalar field are investigated and it has been shown that the ghost instability and gradient instability do not exist.

Proton Radiotherapy for Solid Tumors of Childhood

PubMed Central

Cotter, Shane E.; McBride, Sean M.; Yock, Torunn I.

2012-01-01

The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates. PMID:22417062

Better late than never: information retrieval from black holes.

PubMed

Braunstein, Samuel L; Pirandola, Stefano; Życzkowski, Karol

2013-03-08

We show that, in order to preserve the equivalence principle until late times in unitarily evaporating black holes, the thermodynamic entropy of a black hole must be primarily entropy of entanglement across the event horizon. For such black holes, we show that the information entering a black hole becomes encoded in correlations within a tripartite quantum state, the quantum analogue of a one-time pad, and is only decoded into the outgoing radiation very late in the evaporation. This behavior generically describes the unitary evaporation of highly entangled black holes and requires no specially designed evolution. Our work suggests the existence of a matter-field sum rule for any fundamental theory.

Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

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

Manning, Casey M.; Johnston, Carl J.; Department of Pediatrics, University of Rochester Medical Center, Rochester, New York

2013-05-01

Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infectionmore » and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.« less

A study on differences between radiation-induced micronuclei and apoptosis of lymphocytes in breast cancer patients after radiotherapy.

PubMed

Taghavi-Dehaghani, Mahnaz; Mohammadi, Shahla; Ziafazeli, Tahereh; Sardari-Kermani, Manouchehr

2005-01-01

Cancer patients' responses to radiotherapy vary in severity. It has been suggested that it may be due to differences in intrinsic cellular radiosensitivity. Prediction of tissue reactions to radiotherapy would permit tailoring of dosage to each patient. Towards this goal the micronucleus and apoptosis tests have been proposed as methods for measurement of chromosomal damage in peripheral blood lymphocytes. In this study, gamma-ray sensitivity of cultured lymphocytes of 26 breast cancer patients with early or late reactions was investigated. After irradiation with 4 Gy gamma radiation in G0, the frequency of micronuclei for patients with early reactions was significantly higher (P < 0.05) than for patients with late reactions. In the contrary the frequency of apoptosis for patients with early reactions was significantly lower (P < 0.05) than in the other group. It could be suggested that such a reduced amount of micronuclei in the late effects group is due to the presence of some residual DNA damages which are not completely repaired and lesions show increasing severity when the patients' cells are irradiated again. These induced damages, probably are high enough to stimulate other endpoints like apoptosis instead of micronuclei.

LifeSat - A new research vehicle

NASA Technical Reports Server (NTRS)

Gilbreath, William P.; Dunning, Robert W.

1990-01-01

LifeSat is a reusable recoverable satellite that will support research in the gravitation and radiation biology fields. It can provide sustained lower gravitational levels than manned vehicles and can access orbits where specimens can be exposed to cosmic radiation. The satellite design encompasses environmental support for vertebrate, invertebrate and plant specimens ranging from cells and tissues up to small mammals. The first launch, in a series of 7 satellite flights, is planned for late 1995.

Late evolution of very low mass X-ray binaries sustained by radiation from their primaries

NASA Technical Reports Server (NTRS)

Ruderman, M.; Shaham, J.; Tavani, M.; Eichler, D.

1989-01-01

The accretion-powered radiation from the X-ray pulsar system Her X-1 (McCray et al. 1982) is studied. The changes in the soft X-ray and gamma-ray flux and in the accompanying electron-positron wind are discussed. These are believed to be associated with the inward movement of the inner edge of the accretion disk corresponding to the boundary with the neutron star's corotating magnetosphere (Alfven radius). LMXB evolution which is self-sustained by secondary winds intercepting the radiation emitted near an LMXB neutron star is investigated as well.

Earth Radiation Budget Experiment (ERBE) validation

NASA Technical Reports Server (NTRS)

Barkstrom, Bruce R.; Harrison, Edwin F.; Smith, G. Louis; Green, Richard N.; Kibler, James F.; Cess, Robert D.

1990-01-01

During the past 4 years, data from the Earth Radiation Budget Experiment (ERBE) have been undergoing detailed examination. There is no direct source of groundtruth for the radiation budget. Thus, this validation effort has had to rely heavily upon intercomparisons between different types of measurements. The ERBE SCIENCE Team chose 10 measures of agreement as validation criteria. Late in August 1988, the Team agreed that the data met these conditions. As a result, the final, monthly averaged data products are being archived. These products, their validation, and some results for January 1986 are described. Information is provided on obtaining the data from the archive.

Normal tissue toxicity after small field hypofractionated stereotactic body radiation.

PubMed

Milano, Michael T; Constine, Louis S; Okunieff, Paul

2008-10-31

Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics.

NASA Models of Space Radiation Induced Cancer, Circulatory Disease, and Central Nervous System Effects

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Chappell, Lori J.; Kim, Myung-Hee Y.

2013-01-01

The risks of late effects from galactic cosmic rays (GCR) and solar particle events (SPE) are potentially a limitation to long-term space travel. The late effects of highest concern have significant lethality including cancer, effects to the central nervous system (CNS), and circulatory diseases (CD). For cancer and CD the use of age and gender specific models with uncertainty assessments based on human epidemiology data for low LET radiation combined with relative biological effectiveness factors (RBEs) and dose- and dose-rate reduction effectiveness factors (DDREF) to extrapolate these results to space radiation exposures is considered the current "state-of-the-art". The revised NASA Space Risk Model (NSRM-2014) is based on recent radio-epidemiology data for cancer and CD, however a key feature of the NSRM-2014 is the formulation of particle fluence and track structure based radiation quality factors for solid cancer and leukemia risk estimates, which are distinct from the ICRP quality factors, and shown to lead to smaller uncertainties in risk estimates. Many persons exposed to radiation on earth as well as astronauts are life-time never-smokers, which is estimated to significantly modify radiation cancer and CD risk estimates. A key feature of the NASA radiation protection model is the classification of radiation workers by smoking history in setting dose limits. Possible qualitative differences between GCR and low LET radiation increase uncertainties and are not included in previous risk estimates. Two important qualitative differences are emerging from research studies. The first is the increased lethality of tumors observed in animal models compared to low LET radiation or background tumors. The second are Non- Targeted Effects (NTE), which include bystander effects and genomic instability, which has been observed in cell and animal models of cancer risks. NTE's could lead to significant changes in RBE and DDREF estimates for GCR particles, and the potential effectiveness of radiation mitigator's. The NSRM- 2014 approaches to model radiation quality dependent lethality and NTE's will be described. CNS effects include both early changes that may occur during long space missions and late effects such as Alzheimer's disease (AD). AD effects 50% of the population above age 80-yr, is a degenerative disease that worsens with time after initial onset leading to death, and has no known cure. AD is difficult to detect at early stages and the small number of low LET epidemiology studies undertaken have not identified an association with low dose radiation. However experimental studies in mice suggest GCR may lead to early onset AD. We discuss modeling approaches to consider mechanisms whereby radiation would lead to earlier onset of occurrence of AD. Biomarkers of AD include amyloid beta (A(Beta)) plaques, and neurofibrillary tangles (NFT) made up of aggregates of the hyperphosphorylated form of the micro-tubule associated, tau protein. Related markers include synaptic degeneration, dentritic spine loss, and neuronal cell loss through apoptosis. Radiation may affect these processes by causing oxidative stress, aberrant signaling following DNA damage, and chronic neuroinflammation. Cell types to be considered in multi-scale models are neurons, astrocytes, and microglia. We developed biochemical and cell kinetics models of DNA damage signaling related to glycogen synthase kinase-3(Beta) (GSK3(Beta)) and neuroinflammation, and considered multi-scale modeling approaches to develop computer simulations of cell interactions and their relationships to A(Beta) plaques and NFTs. Comparison of model results to experimental data for the age specific development of A(Beta) plaques in transgenic mice will be discussed.

Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone oligometastases

PubMed Central

Owen, Dawn; Laack, Nadia N.; Mayo, Charles S.; Garces, Yolanda I.; Park, Sean S.; Bauer, Heather J.; Nelson, Kathryn; Miller, Robert W.; Brown, Paul D.; Olivier, Kenneth R.

2015-01-01

Purpose Stereotactic body radiation therapy (SBRT) is being applied more widely for oligometastatic disease. This technique is now being used for non-spine bony metastases in addition to liver, spine, and lung. However, there are few studies examining the toxicity and outcomes of SBRT for non-spine bone metastases. Methods and Materials Between 2008 and 2012, 74 subjects with oligometastatic non-spine bony metastases of varying histologies were treated at the Mayo Clinic with SBRT. A total of 85 non-spine bony sites were treated. Median local control, overall survival, and progression-free survival were described. Acute toxicity (defined as toxicity <90 days) and late toxicity (defined as toxicity ≥90 days) were reported and graded as per standardized Common Toxicity Criteria for Adverse Events 4.0 criteria. Results The median age of patients treated was 60 years. The most common histology was prostate cancer (31%) and most patients had fewer than 3 sites of disease at the time of simulation (64%). Most of the non-spine bony sites lay within the pelvis (65%). Dose and fractionation varied but the most common prescription was 24 Gy/1 fraction. Local recurrence occurred in 7 patients with a median time to failure of 2.8 months. Local control was 91.8% at 1 year. With a median follow-up of 7.6 months, median SBRT specific overall survival and progression-free survival were 9.3 months and 9.7 months, respectively. Eighteen patients developed acute toxicity (mostly grade 1 and 2 fatigue and acute pain flare); 9 patients developed grade 1–2 late toxicities. Two patients developed pathologic fractures but both were asymptomatic. There were no late grade 3 or 4 toxicities. Conclusions Stereotactic body radiation therapy is a feasible and tolerable treatment for non-spine bony metastases. Longer follow-up will be needed to accurately determine late effects. PMID:24890360

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

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

Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.

1994-07-01

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through amore » 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.« less

Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

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

Deville, Curtiland, E-mail: deville@uphs.upenn.ed; Both, Stefan; Hwang, Wei-Ting

2010-11-01

Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinalmore » (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.« less

Radiation Dose-Volume Effects in the Stomach and Small Bowel

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

Kavanagh, Brian D., E-mail: Brian.Kavanagh@ucdenver.ed; Pan, Charlie C.; Dawson, Laura A.

2010-03-01

Published data suggest that the risk of moderately severe (>=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely relatedmore » to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.« less

Climate Change Implications to Vegetation Production in Alaska

NASA Technical Reports Server (NTRS)

Neigh, Christopher S.R.

2008-01-01

Investigation of long-term meteorological satellite data revealed statistically significant vegetation response to climate drivers of temperature, precipitation and solar radiation with exclusion of fire disturbance in Alaska. Abiotic trends were correlated to satellite remote sensing observations of normalized difference vegetation index to understand biophysical processes that could impact ecosystem carbon storage. Warming resulted in disparate trajectories for vegetation growth due to precipitation and photosynthetically active radiation variation. Interior spruce forest low lands in late summer through winter had precipitation deficit which resulted in extensive fire disturbance and browning of undisturbed vegetation with reduced post-fire recovery while Northern slope moist alpine tundra had increased production due to warmer-wetter conditions during the late 1990s and early 2000s. Coupled investigation of Alaska s vegetation response to warming climate found spatially dynamic abiotic processes with vegetation browning not a result from increased fire disturbance.

Treatment of Head and Neck Paragangliomas With External Beam Radiation Therapy

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

Dupin, Charles, E-mail: c.dupin@bordeaux.unicancer.fr; Lang, Philippe; Dessard-Diana, Bernadette

2014-06-01

Purpose: To retrospectively assess the outcomes of radiation therapy in patients with head and neck paragangliomas. Methods and Materials: From 1990 to 2009, 66 patients with 81 head and neck paragangliomas were treated by conventional external beam radiation therapy in 25 fractions at a median dose of 45 Gy (range, 41.4-68 Gy). One case was malignant. The median gross target volume and planning target volume were 30 cm{sup 3} (range, 0.9-243 cm{sup 3}) and 116 cm{sup 3} (range, 24-731 cm{sup 3}), respectively. Median age was 57.4 years (range, 15-84 years). Eleven patients had multicentric lesions, and 8 had family histories ofmore » paraganglioma. Paragangliomas were located in the temporal bone, the carotid body, and the glomus vagal in 51, 18, and 10 patients, respectively. Forty-six patients had exclusive radiation therapy, and 20 had salvage radiation therapy. The median follow-up was 4.1 years (range, 0.1-21.2 years). Results: One patient had a recurrence of temporal bone paraganglioma 8 years after treatment. The actuarial local control rates were 100% at 5 years and 98.7% at 10 years. Patients with multifocal tumors and family histories were significantly younger (42 years vs 58 years [P=.002] and 37 years vs 58 years [P=.0003], respectively). The association between family predisposition and multifocality was significant (P<.001). Two patients had cause-specific death within the 6 months after irradiation. During radiation therapy, 9 patients required hospitalization for weight loss, nausea, mucositis, or ophthalmic zoster. Two late vascular complications occurred (middle cerebral artery and carotid stenosis), and 2 late radiation-related meningiomas appeared 15 and 18 years after treatment. Conclusion: Conventional external beam radiation therapy is an effective and safe treatment option that achieves excellent local control; it should be considered as a first-line treatment of choice for head and neck paragangliomas.« less

Assessing the Impact of Air Pollution on Grain Yield of Winter Wheat - A Case Study in the North China Plain

PubMed Central

Zhang, Xiying; Shao, Liwei; Chen, Suying

2016-01-01

The major wheat production region of China the North China Plain (NCP) is seriously affected by air pollution. In this study, yield of winter wheat (Triticum aestivum L.) was analyzed with respect to the potential impact of air pollution index under conditions of optimal crop management in the NCP from 2001 to 2012. Results showed that air pollution was especially serious at the early phase of winter wheat growth significantly influencing various weather factors. However, no significant correlations were found between final grain yield and the weather factors during the early growth phase. In contrast, significant correlations were found between grain yield and total solar radiation gap, sunshine hour gap, diurnal temperature range and relative humidity during the late growing phase. To disentangle the confounding effects of various weather factors, and test the isolated effect of air pollution induced changes in incoming global solar radiation on yield under ceteris paribus conditions, crop model based scenario-analysis was conducted. The simulation results of the calibrated Agricultural Production Systems Simulator (APSIM) model indicated that a reduction in radiation by 10% might cause a yield reduction by more than 10%. Increasing incident radiation by 10% would lead to yield increases of (only) 7%, with the effects being much stronger during the late growing phase compared to the early growing phase. However, there is evidence that APSIM overestimates the effect of air pollution induced changes on radiation, as it does not consider the changes in radiative properties of solar insulation, i.e. the relative increase of diffuse over direct radiation, which may partly alleviate the negative effects of reduced total radiation by air pollution. Concluding, the present study could not detect a significantly negative effect of air pollution on wheat yields in the NCP. PMID:27612146

Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

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

Chapman, Christopher H., E-mail: chchap@umich.edu; Nagesh, Vijaya; Sundgren, Pia C.

Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results:more » In both structures, longitudinal diffusivity ({lambda}{sub Double-Vertical-Line }) decreased and perpendicular diffusivity ({lambda}{sub Up-Tack }) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum {lambda}{sub Up-Tack} at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in {lambda}{sub Up-Tack} at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum {lambda}{sub Double-Vertical-Line} (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum {lambda}{sub Double-Vertical-Line} changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.« less

Pelvic radiotherapy in the setting of rheumatoid arthritis: Refining the paradigm.

PubMed

Felefly, T; Mazeron, R; Huertas, A; Canova, C H; Maroun, P; Kordahi, M; Morice, P; Deutsch, É; Haie-Méder, C; Chargari, C

2017-04-01

Conflicting results concerning the toxicity of radiotherapy in the setting of rheumatoid arthritis were reported in literature. This work describes the toxicity profiles of patients with rheumatoid arthritis undergoing pelvic radiotherapy for gynecologic malignancies at our institution. Charts of patients with rheumatoid arthritis who underwent pelvic radiotherapy for cervical or endometrial cancer in a curative intent at the Gustave-Roussy Cancer Campus between 1990 and 2015 were reviewed for treatment-related toxicities. Acute and late effects were graded as per the Common Terminology Criteria for Adverse Events version 4.0 scoring system. Eight patients with cervical cancer and three with endometrial cancer were identified. Median follow-up was 56 months. Median external beam radiotherapy dose was 45Gy. All patients received a brachytherapy boost using either pulse- or low-dose rate technique. Concomitant chemotherapy was used in seven cases. Median time from rheumatoid arthritis diagnosis to external beam radiation therapy was 5 years. No severe acute gastrointestinal or genitourinary toxicity was reported. One patient had grade 3 dermatitis. Any late toxicity occurred in 7 /11 patients, and one patient experienced severe late toxicities. One patient with overt systemic rheumatoid arthritis symptoms at the time of external beam radiation therapy experienced late grade 3 ureteral stenosis, enterocolitis and lumbar myelitis. Pelvic radiotherapy, in the setting of rheumatoid arthritis, appears to be feasible, with potentially slight increase in low grade late events compared to other anatomic sites. Patients with overt systemic rheumatoid arthritis manifestation at the time of radiotherapy might be at risk of potential severe toxicities. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Dose–volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment

PubMed Central

Mazzola, R; Ricchetti, F; Fiorentino, A; Fersino, S; Giaj Levra, N; Naccarato, S; Sicignano, G; Albanese, S; Di Paola, G; Alterio, D; Ruggieri, R

2014-01-01

Objective: Dysphagia remains a side effect influencing the quality of life of patients with head and neck cancer (HNC) after radiotherapy. We evaluated the relationship between planned dose involvement and acute and late dysphagia in patients with HNC treated with intensity-modulated radiation therapy (IMRT), after a recontouring of constrictor muscles (PCs) and the cricopharyngeal muscle (CM). Methods: Between December 2011 and December 2013, 56 patients with histologically proven HNC were treated with IMRT or volumetric-modulated arc therapy. The PCs and CM were recontoured. Correlations between acute and late toxicity and dosimetric parameters were evaluated. End points were analysed using univariate logistic regression. Results: An increasing risk to develop acute dysphagia was observed when constraints to the middle PCs were not respected [mean dose (Dmean) ≥50 Gy, maximum dose (Dmax) >60 Gy, V50 >70% with a p = 0.05]. The superior PC was not correlated with acute toxicity but only with late dysphagia. The inferior PC was not correlated with dysphagia; for the CM only, Dmax >60 Gy was correlated with acute dysphagia ≥ grade 2. Conclusion: According to our analysis, the superior PC has a major role, being correlated with dysphagia at 3 and 6 months after treatments; the middle PC maintains this correlation only at 3 months from the beginning of radiotherapy, but it does not have influence on late dysphagia. The inferior PC and CM have a minimum impact on swallowing symptoms. Advances in knowledge: We used recent guidelines to define dose constraints of the PCs and CM. Two results emerge in the present analysis: the superior PC influences late dysphagia, while the middle PC influences acute dysphagia. PMID:25348370

Advances in Therapeutic Development for Radiation Cystitis.

PubMed

Rajaganapathy, Bharathi Raja; Jayabalan, Nirmal; Tyagi, Pradeep; Kaufman, Jonathan; Chancellor, Michael B

2014-01-01

Radiation treatment for pelvic malignancies is typically associated with radiation injury to urinary bladder that can ultimately lead to radiation cystitis (RC). The late sequelae of radiation therapy may take many years to develop and include bothersome storage symptoms such as hematuria, which may be life-threatening in severe cases of hemorrhagic cystitis. Although no definitive treatment is currently available, various interventions are used for radiation and hemorrhagic cystitis including blood transfusion, bladder irrigation, intravesical instillation of substances such as alum, silver nitrate, prostaglandins or formalin, and fulguration of intravesical bleeding sites and surgery options such as supravesical urinary diversions and cystectomy. Effects of non-surgical treatments for radiation and hemorrhagic cystitis are of modest success and studies are lacking to control the effects caused by RC. When such measures have proven ineffective, use of bladder botulinum toxin injection has been reported. New therapy, such as intravesical immunosuppression with local tacrolimus formulation is being developed for the treatment of radiation hemorrhagic cystitis. © 2013 Wiley Publishing Asia Pty Ltd.

Radiobiological impact of reduced margins and treatment technique for prostate cancer in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP).

PubMed

Jensen, Ingelise; Carl, Jesper; Lund, Bente; Larsen, Erik H; Nielsen, Jane

2011-01-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on the Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications. Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates.

PubMed

Andrews, Rachel N; Metheny-Barlow, Linda J; Peiffer, Ann M; Hanbury, David B; Tooze, Janet A; Bourland, J Daniel; Hampson, Robert E; Deadwyler, Samuel A; Cline, J Mark

2017-05-01

Fractionated whole-brain irradiation (fWBI) is a mainstay of treatment for patients with intracranial neoplasia; however late-delayed radiation-induced normal tissue injury remains a major adverse consequence of treatment, with deleterious effects on quality of life for affected patients. We hypothesize that cerebrovascular injury and remodeling after fWBI results in ischemic injury to dependent white matter, which contributes to the observed cognitive dysfunction. To evaluate molecular effectors of radiation-induced brain injury (RIBI), real-time quantitative polymerase chain reaction (RT-qPCR) was performed on the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46), hippocampus and temporal white matter of 4 male Rhesus macaques (age 6-11 years), which had received 40 Gray (Gy) fWBI (8 fractions of 5 Gy each, twice per week), and 3 control comparators. All fWBI animals developed neurologic impairment; humane euthanasia was elected at a median of 6 months. Radiation-induced brain injury was confirmed histopathologically in all animals, characterized by white matter degeneration and necrosis, and multifocal cerebrovascular injury consisting of perivascular edema, abnormal angiogenesis and perivascular extracellular matrix deposition. Herein we demonstrate that RIBI is associated with white matter-specific up-regulation of hypoxia-associated lactate dehydrogenase A (LDHA) and that increased gene expression of fibronectin 1 (FN1), SERPINE1 and matrix metalloprotease 2 (MMP2) may contribute to cerebrovascular remodeling in late-delayed RIBI. Additionally, vascular stability and maturation associated tumor necrosis super family member 15 (TNFSF15) and vascular endothelial growth factor beta (VEGFB) mRNAs were increased within temporal white matter. We also demonstrate that radiation-induced brain injury is associated with decreases in white matter-specific expression of neurotransmitter receptors SYP, GRIN2A and GRIA4. We additionally provide evidence that macrophage/microglial mediated neuroinflammation may contribute to RIBI through increased gene expression of the macrophage chemoattractant CCL2 and macrophage/microglia associated CD68. Global patterns in cerebral gene expression varied significantly between regions examined (P < 0.0001, Friedman's test), with effects most prominent within cerebral white matter.

Risk of Severe Toxicity According to Site of Recurrence in Patients Treated With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer

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

Ling, Diane C.; Vargo, John A.; Ferris, Robert L.

Purpose: To report a 10-year update of our institutional experience with stereotactic body radiation therapy (SBRT) for reirradiation of locally recurrent head and neck cancer, focusing on predictors of toxicity. Methods and Materials: A retrospective review was performed on 291 patients treated with SBRT for recurrent, previously irradiated head and neck cancer between April 2002 and March 2013. Logistic regression analysis was performed to identify predictors of severe acute and late toxicity. Patients with <3 months of follow-up (n=43) or who died within 3 months of treatment (n=21) were excluded from late toxicity analysis. Results: Median time to death or last clinicalmore » follow-up was 9.8 months among the entire cohort and 53.1 months among surviving patients. Overall, 33 patients (11.3%) experienced grade ≥3 acute toxicity and 43 (18.9%) experienced grade ≥3 late toxicity. Compared with larynx/hypopharynx, treatment of nodal recurrence was associated with a lower risk of severe acute toxicity (P=.03), with no significant differences in severe acute toxicity among other sites. Patients treated for a recurrence in the larynx/hypopharynx experienced significantly more severe late toxicity compared with those with oropharyngeal, oral cavity, base of skull/paranasal sinus, salivary gland, or nodal site of recurrence (P<.05 for all). Sixteen patients (50%) with laryngeal/hypopharyngeal recurrence experienced severe late toxicity, compared with 6-20% for other sites. Conclusions: Salvage SBRT is a safe and effective option for most patients with previously irradiated head and neck cancer. However, patients treated to the larynx or hypopharynx experience significantly more late toxicity compared with others and should be carefully selected for treatment, with consideration given to patient performance status, pre-existing organ dysfunction, and goals of care. Treatment toxicity in these patients may be mitigated with more conformal plans to allow for increased sparing of adjacent normal tissues.« less

Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522

PubMed Central

Ang, K. Kian; Zhang, Qiang; Rosenthal, David I.; Nguyen-Tan, Phuc Felix; Sherman, Eric J.; Weber, Randal S.; Galvin, James M.; Bonner, James A.; Harris, Jonathan; El-Naggar, Adel K.; Gillison, Maura L.; Jordan, Richard C.; Konski, Andre A.; Thorstad, Wade L.; Trotti, Andy; Beitler, Jonathan J.; Garden, Adam S.; Spanos, William J.; Yom, Sue S.; Axelrod, Rita S.

2014-01-01

Purpose Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Patients and Methods Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Results Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v 2.0%, respectively; P = .81), 3-year PFS (61.2% v 58.9%, respectively; P = .76), 3-year OS (72.9% v 75.8%, respectively; P = .32), locoregional failure (19.9% v 25.9%, respectively; P = .97), or distant metastasis (13.0% v 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v 49.2%, respectively; P < .001) and OS (85.6% v 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Conclusion Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression. PMID:25154822

Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522.

PubMed

Ang, K Kian; Zhang, Qiang; Rosenthal, David I; Nguyen-Tan, Phuc Felix; Sherman, Eric J; Weber, Randal S; Galvin, James M; Bonner, James A; Harris, Jonathan; El-Naggar, Adel K; Gillison, Maura L; Jordan, Richard C; Konski, Andre A; Thorstad, Wade L; Trotti, Andy; Beitler, Jonathan J; Garden, Adam S; Spanos, William J; Yom, Sue S; Axelrod, Rita S

2014-09-20

Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v. 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v. 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v. 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v. 2.0%, respectively; P = .81), 3-year PFS (61.2% v. 58.9%, respectively; P = .76), 3-year OS (72.9% v. 75.8%, respectively; P = .32), locoregional failure (19.9% v. 25.9%, respectively; P = .97), or distant metastasis (13.0% v. 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v. 49.2%, respectively; P < .001) and OS (85.6% v. 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.

Space radiation and cataracts in astronauts.

PubMed

Cucinotta, F A; Manuel, F K; Jones, J; Iszard, G; Murrey, J; Djojonegro, B; Wear, M

2001-11-01

For over 30 years, astronauts in Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons and heavy ions and secondary particles produced in collisions with spacecraft and tissue. Large uncertainties exist in the projection of risks of late effects from space radiation such as cancer and cataracts due to the paucity [corrected] of epidemiological data. Here we present epidemiological [corrected] data linking an increased risk of cataracts for astronauts with higher lens doses (>8 mSv) of space radiation relative to other astronauts with lower lens doses (<8 mSv). Our study uses historical data for cataract incidence in the 295 astronauts participating in NASA's Longitudinal Study of Astronaut Health (LSAH) and individual occupational radiation exposure data. These results, while preliminary because of the use of subjective scoring methods, suggest that relatively low doses of space radiation may predispose crew to [corrected] an increased incidence and early appearance of cataracts.

Space radiation and cataracts in astronauts

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Manuel, F. K.; Jones, J.; Iszard, G.; Murrey, J.; Djojonegro, B.; Wear, M.

2001-01-01

For over 30 years, astronauts in Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons and heavy ions and secondary particles produced in collisions with spacecraft and tissue. Large uncertainties exist in the projection of risks of late effects from space radiation such as cancer and cataracts due to the paucity [corrected] of epidemiological data. Here we present epidemiological [corrected] data linking an increased risk of cataracts for astronauts with higher lens doses (>8 mSv) of space radiation relative to other astronauts with lower lens doses (<8 mSv). Our study uses historical data for cataract incidence in the 295 astronauts participating in NASA's Longitudinal Study of Astronaut Health (LSAH) and individual occupational radiation exposure data. These results, while preliminary because of the use of subjective scoring methods, suggest that relatively low doses of space radiation may predispose crew to [corrected] an increased incidence and early appearance of cataracts.

Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits.

PubMed

Krukowski, Karen; Feng, Xi; Paladini, Maria Serena; Chou, Austin; Sacramento, Kristen; Grue, Katherine; Riparip, Lara-Kirstie; Jones, Tamako; Campbell-Beachler, Mary; Nelson, Gregory; Rosi, Susanna

2018-05-18

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation can cause long-term cognitive impairments in rodent models thereby presenting potential obstacles for astronauts engaged in deep space travel. The mechanism/s for how cosmic radiation induces cognitive deficits are currently unknown. We find that temporary microglia depletion, one week after cosmic radiation, prevents the development of long-term memory deficits. Gene array profiling reveals that acute microglia depletion alters the late neuroinflammatory response to cosmic radiation. The repopulated microglia present a modified functional phenotype with reduced expression of scavenger receptors, lysosome membrane protein and complement receptor, all shown to be involved in microglia-synapses interaction. The lower phagocytic activity observed in the repopulated microglia is paralleled by improved synaptic protein expression. Our data provide mechanistic evidence for the role of microglia in the development of cognitive deficits after cosmic radiation exposure.

Total ozone influence on the surface UV-B radiation in the late spring-summer 1963-1997: An analysis of multiple timescales

NASA Astrophysics Data System (ADS)

KrzyśCin, Janusz W.

2000-02-01

Monthly means and minima of total ozone for the late springs and summers (May-August) of 1963-1997 have been examined for the European Dobson stations (Arosa, Belsk, Hohenpeissenberg, Hradec Kralove, Uccle). It is shown that long-term tendencies in total ozone means were almost similar to those in the total ozone minima. Analyses of the late spring/summer means of UV daily doses, total ozone, and global solar radiation (proxy for the overall atmospheric transparency), measured at Belsk (52°N, 21°E) for the period 1976-1996, show that an importance of the total ozone changes for the UV-B level increases with the timescale. Decadal variations in total ozone are the main source of the UV trend at Belsk. Frequency of appearance of extreme daily total ozone values in the selected late spring/summer season seems to be important for analyses of the ozone forcing in the interannual timescale. Regional and temporal differences in the number of days with extreme low ozone values are discussed using the total ozone extrema taken at Arosa, Belsk, and Hradec Kralove in the 1963-1997 period. A statistical model is developed for diagnosis of the next day value of the UV-B level. The changes in the overall atmospheric transparency are essential for the UV-B level when the day-to-day variations in the UV forcing factors are examined.

Epidemiology of Late Health Effects in Ukrainian Chornobyl Cleanup Workers.

PubMed

Bazyka, Dimitry; Prysyazhnyuk, Anatoly; Gudzenko, Natalya; Dyagil, Iryna; Belyi, David; Chumak, Vadim; Buzunov, Volodymyr

2018-07-01

This article summarizes the results of 30 y of follow-up of cancer and noncancer effects in Ukrainian cleanup workers after the Chornobyl accident. The number of power plant employees and first responders with acute radiation syndrome under follow-up by the National Research Center for Radiation Medicine decreased from 179 in 1986-1991 to 105 in 2011-2015. Cancers and leukemia (19) and cardiovascular diseases (21) were the main causes of deaths among acute radiation syndrome survivors (54) during the postaccident period. Increased radiation risks of leukemia in the Ukrainian cohort of 110,645 cleanup workers exposed to low doses are comparable to those among survivors of the atomic bomb explosions in Japan in 1945. Additionally, an excess of chronic lymphocytic leukemia was demonstrated in the cleanup workers cohort for 26 y after the exposure. A significant excess of multiple myeloma incidence [standardized incidence rate (SIR) 1.61 %, 95% confidence interval (CI) 1.01-2.21], thyroid cancer (SIR 4.18, 95% CI 3.76-4.59), female breast cancer (SIR 1.57 CI 1.40-1.73), and all cancers combined (SIR 1.07; 95% CI 1.05-1.09) was registered. High prevalence was demonstrated for cardio- and cerebrovascular diseases and mental health changes. However, the reasons for the increases require further investigation. To monitor other possible late effects of radiation exposure in Chornobyl cleanup workers, analytical cohort and case-control studies need to include cardiovascular pathology, specifically types of potentially radiogenic cancers using a molecular epidemiology approach. Possible effects for further study include increased rates of thyroid, breast, and lung cancers and multiple myeloma; reduction of radiation risks of leukemia to population levels; and increased morbidity and mortality of cleanup workers from cardio- and cerebrovascular pathology.

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

Hoppe, Bradford S.; Stegman, Lauren D.; Zelefsky, Michael J.

Purpose: To perform a retrospective analysis of patients with paranasal sinus (PNS) cancer treated with postoperative radiotherapy (RT) at Memorial Sloan-Kettering Cancer Center. Methods and Materials: Between January 1987 and July 2005, 85 patients with PNS and nasal cavity cancer underwent postoperative RT. Most patients had squamous cell carcinoma (49%; n = 42), T4 tumors (52%; n = 36), and the maxillary sinus (53%; n = 45) as the primary disease site. The median radiation dose was 63 Gy. Of the 85 patients, 76 underwent CT simulation and 53 were treated with either three-dimensional conformal RT (27%; n = 23)more » or intensity-modulated RT (35%; n = 30). Acute and late toxicities were scored according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Results: With a median follow-up for surviving patients of 60 months, the 5-year estimates of local progression-free, regional progression-free, distant metastasis-free, disease-free, and overall survival rates were 62%, 87%, 82%, 55%, and 67%, respectively. On multivariate analysis, squamous cell histology and cribriform plate involvement predicted for an increased likelihood of local recurrence, and squamous cell histologic features predicted for worse overall survival. None of the patients who underwent CT simulation and were treated with modern techniques developed a Grade 3-4 late complication of the eye. Conclusion: Complete surgical resection followed by adjuvant RT is an effective and safe approach in the treatment of PNS cancer. Emerging tools, such as three-dimensional conformal treatment and, in particular, intensity-modulated RT for PNS tumors, may minimize the occurrence of late complications associated with conventional RT techniques. Local recurrence remains a significant problem.« less

Fusion of Ultrasound Tissue-Typing Images with Multiparametric MRI for Image-guided Prostate Cancer Radiation Therapy

DTIC Science & Technology

2014-10-01

work under the guidance of an outstanding mentor team at Emory Winship Cancer Institute. I took three courses ( Medical Health Physics, Radiation...and Late Normal-Tissue Toxicity in Breast- Cancer Radiotherapy”, Medical Physics, 40(6):379, 2013. 5. Yang X, Liu T, Curran W and Torres M...Analysis for Normal-tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast- Cancer Radiotherapy", Medical Physics 41 (6), 482-482

Postharvest irradiation treatment for quarantine control of Drosophila suzukii (Diptera: Drosophilidae) in fresh commodities.

PubMed

Follett, Peter A; Swedman, Allison; Prices, Donald K

2014-06-01

Irradiation is a postharvest quarantine treatment option for exported commodities such as stone fruits and small fruits to prevent movement of the new invasive pest spotted wing drosophila, Drosophila suzukii (Walker) (Diptera: Drosophilidae). The effects of irradiation on larval and pupal development and adult reproduction in D. suzukii were examined. Larvae (first, second, and third instars) and pupae (1-2-d-old, 3-5-d-old, and 7-8-d-old) on diet were irradiated at target doses of 20, 30, 40, and 50 Gy in replicated factorial experiments and survival to the adult stage was recorded. Tolerance to radiation increased with increasing age and developmental stage. Males and females were equally susceptible. A radiation dose of 40 Gy applied to first- and second-instar larvae prevented adult emergence. The late-stage pupa was the most radiation-tolerant stage that occurs in fruit, and individuals irradiated at this stage readily emerged as adults; therefore, prevention of F1 adults was the desired treatment response for large-scale validation tests with naturally infested fruit. In large-scale tests, a radiation dose of 80 Gy applied to late-stage pupae in sweet cherries or grapes resulted in no production of F1 adults in > 33,000 treated individuals, which meets the zero tolerance requirement for market access. A minimum absorbed dose of 80 Gy is recommended for quarantine control of D. suzukii.

Radiotherapy after surgical resection for head and neck mucosal melanoma.

PubMed

Wu, Abraham J; Gomez, Jennifer; Zhung, Joanne E; Chan, Kelvin; Gomez, Daniel R; Wolden, Suzanne L; Zelefsky, Michael J; Wolchok, Jedd D; Carvajal, Richard D; Chapman, Paul B; Wong, Richard J; Shaha, Ashok R; Kraus, Dennis H; Shah, Jatin P; Lee, Nancy Y

2010-06-01

To present our single-institution experience with postoperative radiotherapy for mucosal melanoma of the head and neck. Between 1992 and 2007, 27 patients with mucosal melanoma of the head and neck underwent surgical resection followed by postoperative radiotherapy. Median age was 68 years (range: 45-89 years). Sites included were sinonasal in 24 patients, oral cavity in 2, and oropharynx in 1. All but 2 patients had stage I disease. Twenty-two patients received hypofractionated radiation. Radiation techniques were intensity-modulated radiation therapy in 13, 3-dimensional conformal in 4, and conventional in 10. The median follow-up for living patients was 45 months (range: 24-122 months). The 3- and 5-year estimates of local progression-free, loco-regional progression-free, distant metastasis-free, and overall survival were: 47% and 35%; 34% and 22%; 30% and 24%; and 40% and 33%, respectively. Median time to local failure and distant metastasis was 32 and 14 months, respectively. Acute toxicities included 19% with grade 2 or higher mucositis. No late complications related to the optic structures were seen. Modern radiotherapeutic techniques including intensity-modulated radiation therapy appear feasible and well-tolerated in the postoperative treatment of head and neck mucosal melanoma. Unusual or serious late complications have not been observed despite extensive use of hypofractionated regimens. However, rates of local and distant failure remain high.

Use of an image-guided robotic radiosurgery system for the treatment of canine nonlymphomatous nasal tumors.

PubMed

Glasser, Seth A; Charney, Sarah; Dervisis, Nikolaos G; Witten, Matthew R; Ettinger, Susan; Berg, Jason; Joseph, Richard

2014-01-01

An image-guided robotic stereotactic radiosurgery (SRS) system can be used to deliver curative-intent radiation in either single fraction or hypofractionated doses. Medical records for 19 dogs with nonlymphomatous nasal tumors treated with hypofractionated image-guided robotic stereotactic body radiotherapy (SBRT), either with or without adjunctive treatment, were retrospectively analyzed for survival and prognostic factors. Median survival time (MST) was evaluated using Kaplan-Meier survival curves. Age, breed, tumor type, stage, tumor size, prescribed radiation dose, and heterogeneity index were analyzed for prognostic significance. Dogs were treated with three consecutive-day, 8-12 gray (Gy) fractions of image-guided robotic SBRT. Overall MST was 399 days. No significant prognostic factors were identified. Acute side effects were rare and mild. Late side effects included one dog with an oronasal fistula and six dogs with seizures. In three of six dogs, seizures were a presenting complaint prior to SBRT. The cause of seizures in the remaining three dogs could not be definitively determined due to lack of follow-up computed tomography (CT) imaging. The seizures could have been related to either progression of disease or late radiation effect. Results indicate that image-guided robotic SBRT, either with or without adjunctive therapy, for canine nonlymphomatous nasal tumors provides comparable survival times (STs) to daily fractionated megavoltage radiation with fewer required fractions and fewer acute side effects.

Tropical shoreline ice in the late Cambrian: Implications for earth's climate between the Cambrian Explosion and the Great Ordovician Biodiversification Event

USGS Publications Warehouse

Runkel, Anthony C.; MacKey, T.J.; Cowan, Clinton A.; Fox, David L.

2010-01-01

Middle to late Cambrian time (ca. 513 to 488 Ma) is characterized by an unstable plateau in biodiversity, when depauperate shelf faunas suffered repeated extinctions. This poorly understood interval separates the Cambrian Explosion from the Great Ordovician Biodiversification Event and is generally regarded as a time of sustained greenhouse conditions. We present evidence that suggests a drastically different climate during this enigmatic interval: Features indicative of meteoric ice are well preserved in late Cambrian equatorial beach deposits that correspond to one of the shelf extinction events. Thus, the middle to late Cambrian Earth was at least episodically cold and might best be considered a muted analogue to the environmental extremes that characterized the Proterozoic, even though cooling in the two periods may have occurred in response to different triggers. Such later Cambrian conditions may have significantly impacted evolution preceding the Ordovician radiation.

Advances in Radiation Mutagenesis through Studies on Drosophila

DOE R&D Accomplishments Database

Muller, H. J.

1958-06-01

The approximately linear relation between radiation dose and induced lethals known for Drosophila spermatozoa, is now extended to spermatids. Data are included regarding oogonia. The linearity principle has been confined for minute structural changes in sperm as multi-hit events, on about the 1.5 power of the dose, long known for spermatozoa, is now extended to spermatids and late oocytes, for relatively short exposures. are found to allow union of broken chromosomes. Therefore, the frequencies are lower for more dispersed exposures of varies with lethals induced in late oocytes follow the same frequency pattern and there fore are multi-hit events. Yet han spermatozoan irradiation that two broken ends derived from nonreciprocal. The following is the order of decreasing radiation mutability of different stages found by ourselves and others: spermatids, spermatozoa in females, spermatozoa 0 to 1 day before ejaculation, earlier spermatozoa, late oocytes, gonia of either sex. Lethal frequencies for these stages range over approximately an order of magnitude, gross structural changes far more widely. Of potential usefulness is our extension of genesis by anoxia, known for spermatozoa in adult males, to those in pupal males and in females, to sperion is especially marked but the increase caused by substituting oxygen for air is less marked, perhaps because of enzymatic differences. In contrast, the induction of gross structural changes in oocytes, but not in spermatids, is markedly reduced by oxygen post-treatment; it is increased by dehydration. The efficacy of induction of structural changes by treatment of spermatozoa, whether with radiation or chemical mutagen, is correlated with the conditions of sperm utilization and egg production. Improving our perspective on radiation effects, some 800,000 offspring have been scored for spontaneous visible mutations of 13 specific loci. The average point-mutation rate was 0.5 to 1.0 per locus among 10/sup 5/ germ cells. Most mutation occurred in peri- fertilization stages. All loci studied mutated from one to nine times. Loci mutating oftener spontaneously also gave more radiation mutation, in other studies, Spectra of individual loci prove similar for spontaneous and induced mutation. Studies on back-mutation also showed similarity of spontaneous and radiation mutations. The doubling dose for back-mutations of forked induced in spermatozoa was several hundred roentgens, gonia at diverse loci. Recent analyses of human mutational load lead to mutation-rate estimated like those earlier based on extrapolations from Drosophila, thus supporting the significance for man of the present studies. (auth)

Evaluation and Development of Radiation Countermeasures at AFRRI

DTIC Science & Technology

2005-01-01

epigallocatechin gallate ( EGCG ), benzyl styryl sulfones, CpG oligonucleotides, a superoxide dismutase mi- metic, statins, dipeptidyl peptidase inhibitors, and...candidate (Hollis-Eden Pharmaceuticals) • Soy isoflavones • Vitamin E-related compounds (Yasoo Health) • Phenylacetate, phenylbutyrate, EGCG (late

Sensitivity of Hawking radiation to superluminal dispersion relations

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

Barcelo, C.; Garay, L. J.; Instituto de Estructura de la Materia, CSIC, Serrano 121, 28006 Madrid

2009-01-15

We analyze the Hawking radiation process due to collapsing configurations in the presence of superluminal modifications of the dispersion relation. With such superluminal dispersion relations, the horizon effectively becomes a frequency-dependent concept. In particular, at every moment of the collapse, there is a critical frequency above which no horizon is experienced. We show that, as a consequence, the late-time radiation suffers strong modifications, both quantitative and qualitative, compared to the standard Hawking picture. Concretely, we show that the radiation spectrum becomes dependent on the measuring time, on the surface gravities associated with different frequencies, and on the critical frequency. Evenmore » if the critical frequency is well above the Planck scale, important modifications still show up.« less

The response of solar radiation in Jubail, Saudi Arabia, to smoke from oil field fires in Kuwait

NASA Astrophysics Data System (ADS)

Riley, James J.; Hicks, Neal G.; Thompson, T. Lewis

1992-09-01

The relative monthly solar radiation in Jubail Industrial City, Saudi Arabia (300 km southeast of Kuwait City) was reduced to 75% of the recent 10-year mean value by the torching of the first 50 of many oil wells and production facilities in Kuwait in mid-January 1991. The value was reduced further when an additional 600 wells were ignited in late February. Solar radiation continued at 55 65% of normal levels during March to August, when 341 oil wells were still burning. Recovery was rapid as the fires in oil fields located directly upwind of Jubail were extinguished, with the solar radiation reaching 95% of the long-term mean in October.

Protective effect of α-lipoic acid against radiation-induced fibrosis in mice

PubMed Central

Ryu, Seung-Hee; Park, Eun-Young; Kwak, Sungmin; Heo, Seung-Ho; Ryu, Je-Won; Park, Jin-hong

2016-01-01

Radiation-induced fibrosis (RIF) is one of the most common late complications of radiation therapy. We found that α-lipoic acid (α-LA) effectively prevents RIF. In RIF a mouse model, leg contracture assay was used to test the in vivo efficacy of α-LA. α-LA suppressed the expression of pro-fibrotic genes after irradiation, both in vivo and in vitro, and inhibited the up-regulation of TGF-β1-mediated p300/CBP activity. Thus, α-LA prevents radiation-induced fibrosis (RIF) by inhibiting the transcriptional activity of NF-κB through inhibition of histone acetyltransferase activity. α-LA is a new therapeutic methods that can be used in the prevention-treatment of RIF. PMID:26799284

Concurrent Cyclophosphamide, Methotrexate, and 5-Fluorouracil Chemotherapy and Radiotherapy for Early Breast Carcinoma

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

Livi, Lorenzo; Saieva, Calogero; Borghesi, Simona

2008-07-01

Purpose: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. Patients and Methods: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m{sup 2}, methotrexate 40 mg/m{sup 2}, and 5-fluorouracil 600 mg/m{sup 2}) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at themore » discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. Results: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). Conclusions: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.« less

Did a Gamma-Ray Burst Initiate the Late Ordovician Mass Extinction?

NASA Technical Reports Server (NTRS)

Melott, A. L.; Lieberman, B. S.; Laird, C. M.; Martin, L. D.; Medvedov, M. V.; Thomas, B. C.; Cannizzo, J. K.; Gehrels, N.; Jackman, C. H.

2004-01-01

Gamma-ray bursts (hereafter GRB) produce a flux of radiation detectable across the observable Universe. A GRB within our own galaxy could do considerable damage to the Earth's biosphere; rate estimates suggest that a dangerously near GRB should occur on average several times per billion years. At leastfive times in the history of lfe, the Earth experienced mass extinctions that eliminated a large percentage of the biota. Many possible causes have been documented, and GRB may also have contributed. The late Ordovician mass extinction approximately 440 million years ago may be at least partly the result of a GRB. Due to severe depletion of the ozone layer, intense solar ultraviolet radiation is expected to result from a nearby GRB, and some of the patterns of extinction and survivorship at this time may be attributable to elevated levels of UV radiation reaching the Earth. In addition a GRB could trigger the global cooling which occurs at the end of the Ordovician period that follows an interval of relatively warm climate. Intense rapid cooling and glaciation at that time, previously identijied as the probable cause of this mass extinction, may have resultedfiom a GRB.

Unexpected evolutionary diversity in a recently extinct Caribbean mammal radiation

PubMed Central

Brace, Selina; Turvey, Samuel T.; Weksler, Marcelo; Hoogland, Menno L. P.; Barnes, Ian

2015-01-01

Identifying general patterns of colonization and radiation in island faunas is often hindered by past human-caused extinctions. The insular Caribbean is one of the only complex oceanic-type island systems colonized by land mammals, but has witnessed the globally highest level of mammalian extinction during the Holocene. Using ancient DNA analysis, we reconstruct the evolutionary history of one of the Caribbean's now-extinct major mammal groups, the insular radiation of oryzomyine rice rats. Despite the significant problems of recovering DNA from prehistoric tropical archaeological material, it was possible to identify two discrete Late Miocene colonizations of the main Lesser Antillean island chain from mainland South America by oryzomyine lineages that were only distantly related. A high level of phylogenetic diversification was observed within oryzomyines across the Lesser Antilles, even between allopatric populations on the same island bank. The timing of oryzomyine colonization is closely similar to the age of several other Caribbean vertebrate taxa, suggesting that geomorphological conditions during the Late Miocene facilitated broadly simultaneous overwater waif dispersal of many South American lineages to the Lesser Antilles. These data provide an important baseline by which to further develop the Caribbean as a unique workshop for studying island evolution. PMID:25904660

The changing role of accelerators in radiation therapy

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

Hanson, W.F.

Conventional low energy x-rays have been used in radiation therapy since the turn of the century. Van de Graaff and Betatron accelerators changed the complexion of radiation therapy in the mid 1940's by providing significantly deeper penetrating photon beams and also providing therapeutic quality electron beams. The development of Cobalt-60 teletherapy in the mid 1950's suppressed the role of accelerators in radiation therapy for nearly 20 years. However, with the development of reliable isocentric rotating linear accelerators, accelerators are rapidly becoming the most popular conventional therapy devices. Following unfavorable clinical results with fast neutron therapy in the late 1930's andmore » early 1940's, the role of cyclotron produced fast neutrons is presently experiencing a renewal in radiation therapy. Several facilities are also experimenting with heavy charged particle beams for therapy.« less

Fistulizing Crohn’s disease: Diagnosis and management

PubMed Central

Gecse, Krisztina; Khanna, Reena; Stoker, Jaap; Jenkins, John T; Gabe, Simon; Hahnloser, Dieter

2013-01-01

Fistulizing Crohn’s disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn’s disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery. PMID:24917961

[Lymphogranuloma venereum].

PubMed

Vaňousová, Daniela; Zákoucká, Hana; Marvan, Jaroslav; Jilich, David; Vojáčková, Naděžda; Hercogová, Jana; Machala, Ladislav

2012-01-01

Lymphogranuloma venereum is a sexually transmitted disease caused by serovars L1-3 of Chlamydia trachomatis. This infection was originally endemic in tropics and transmitted predominantly by heterosexual contact but since the beginning of the century it spreads in industrialized countries mainly among men having sex with men causing them severe proctitis. In the Czech Republic the first case was diagnosed in 2011. Lymphogranuloma venereum can resemble other forms of anorectal disorders inclusive inflammatory bowel diseases and thus it must be included into differential diagnostic considerations. Definitive diagnosis is based on detection of specific serovars of Chlamydia trachomatis by polymerase chain reaction. In patients with lymphogranuloma venereum it is also necessary to exclude other sexually transmitted diseases, particularly syphilis, HIV and also hepatitis C. The therapy of choice is doxycycline administered for three weeks.

Management and Prevention of Breast Cancer After Radiation to the Chest for Childhood, Adolescent, and Young Adulthood Malignancy.

PubMed

Koo, Eva; Henderson, Michael A; Dwyer, Mary; Skandarajah, Anita R

2015-12-01

Women treated with chest irradiation for childhood, adolescent, and young adulthood (CAYA) malignancies, in particular Hodgkin's lymphoma, have an increased risk of developing second cancers of the breast (SCB). However, there are few uniform guidelines regarding surveillance and prevention for this high-risk group. A systematic search using PUBMED and OVID MEDLINE was performed. Publications listed under the terms "breast neoplasm", "neoplasm, radiation-induced", "therapeutic radiation-induced breast cancer", "screening", "surveillance", "prevention", and "prophylaxis" between January 1992 and January 2015 were assessed. A total of 138 publications were reviewed. Factors associated with increased SCB risk include young age at irradiation, prolong duration since irradiation (peak relative risk 13.87 at 15-19 years postradiation), and increased radiation dose and field. Early menopause reduces SCB risk. Annual screening mammography and breast MRI is recommended from age 25 or 8 years posttreatment for women treated with ≥20 Gy chest radiation before age 30 years. Compared with sporadic primary breast cancers (PBC), SCB more often are bilateral (6-34 %), managed with mastectomy (56-100 %), hormone receptor-negative (27-49 %), and high-grade (35 %). Women with SCB have a similar breast cancer event-free survival and breast cancer-specific survival compared to women with PBC. However, their overall survival is worse due to comorbid conditions. There is paucity of information regarding secondary prevention of SCB. Survivors of CAYA malignancy are at risk of many late effects, including iatrogenic breast cancer from chest irradiation. They are best managed in a multidisciplinary late-effects setting where tailored risk management can be provided.

Japanese Legacy Cohorts: The Life Span Study Atomic Bomb Survivor Cohort and Survivors’ Offspring

PubMed Central

Grant, Eric J; Kodama, Kazunori

2018-01-01

Cohorts of atomic bomb survivors—including those exposed in utero—and children conceived after parental exposure were established to investigate late health effects of atomic bomb radiation and its transgenerational effects by the Atomic Bomb Casualty Commission (ABCC) in the 1950s. ABCC was reorganized to the Radiation Effects Research Foundation (RERF) in 1975, and all work has been continued at RERF. The Life Span Study, the cohort of survivors, consists of about 120,000 subjects and has been followed since 1950. Cohorts of in utero survivors and the survivors’ children include about 3,600 and 77,000 subjects, respectively, and have been followed since 1945. Atomic bomb radiation dose was estimated for each subject based on location at the time of the bombing and shielding conditions from exposure, which were obtained through enormous efforts of investigators and cooperation of subjects. Outcomes include vital status, cause of death, and cancer incidence. In addition, sub-cohorts of these three cohorts were constructed to examine clinical features of late health effects, and the subjects have been invited to periodic health examinations at clinics of ABCC and RERF. They were also asked to donate biosamples for biomedical investigations. Epidemiological studies have observed increased radiation risks for malignant diseases among survivors, including those exposed in utero, and possible risks for some non-cancer diseases. In children of survivors, no increased risks due to parental exposure to radiation have been observed for malignancies or other diseases, but investigations are continuing, as these cohorts are still relatively young. PMID:29553058

Japanese Legacy Cohorts: The Life Span Study Atomic Bomb Survivor Cohort and Survivors' Offspring.

PubMed

Ozasa, Kotaro; Grant, Eric J; Kodama, Kazunori

2018-04-05

Cohorts of atomic bomb survivors-including those exposed in utero-and children conceived after parental exposure were established to investigate late health effects of atomic bomb radiation and its transgenerational effects by the Atomic Bomb Casualty Commission (ABCC) in the 1950s. ABCC was reorganized to the Radiation Effects Research Foundation (RERF) in 1975, and all work has been continued at RERF. The Life Span Study, the cohort of survivors, consists of about 120,000 subjects and has been followed since 1950. Cohorts of in utero survivors and the survivors' children include about 3,600 and 77,000 subjects, respectively, and have been followed since 1945. Atomic bomb radiation dose was estimated for each subject based on location at the time of the bombing and shielding conditions from exposure, which were obtained through enormous efforts of investigators and cooperation of subjects. Outcomes include vital status, cause of death, and cancer incidence. In addition, sub-cohorts of these three cohorts were constructed to examine clinical features of late health effects, and the subjects have been invited to periodic health examinations at clinics of ABCC and RERF. They were also asked to donate biosamples for biomedical investigations. Epidemiological studies have observed increased radiation risks for malignant diseases among survivors, including those exposed in utero, and possible risks for some non-cancer diseases. In children of survivors, no increased risks due to parental exposure to radiation have been observed for malignancies or other diseases, but investigations are continuing, as these cohorts are still relatively young.

Generalized uncertainty principle impact onto the black holes information flux and the sparsity of Hawking radiation

NASA Astrophysics Data System (ADS)

Alonso-Serrano, Ana; DÄ browski, Mariusz P.; Gohar, Hussain

2018-02-01

We investigate the generalized uncertainty principle (GUP) corrections to the entropy content and the information flux of black holes, as well as the corrections to the sparsity of the Hawking radiation at the late stages of evaporation. We find that due to these quantum gravity motivated corrections, the entropy flow per particle reduces its value on the approach to the Planck scale due to a better accuracy in counting the number of microstates. We also show that the radiation flow is no longer sparse when the mass of a black hole approaches Planck mass which is not the case for non-GUP calculations.

Radiation Therapy for Oral Cavity and Oropharyngeal Cancers.

PubMed

Lin, Alexander

2018-01-01

Radiotherapy is a key therapeutic modality used in the treatment of oral cavity and oropharyngeal cancers, whether as definitive treatment or postoperatively for those with high-risk factors after surgery. Although radiotherapy is a proven, effective treatment of cancer control, it can result in significant acute and late toxicities. Pretreatment patient education, supportive care, and posttreatment adherence to rehabilitative and preventive care can help mitigate toxicities. Advances in radiation delivery, such as through continued technological advances, or novel approaches to customizing radiation dose and volume, to maximize the therapeutic efficacy while minimizing side effects, are warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Patient Dose In Diagnostic Radiology: When & How?

NASA Astrophysics Data System (ADS)

Lassen, Margit; Gorson, Robert O.

1980-08-01

Different situations are discussed in which it is of value to know radiation dose to the patient in diagnostic radiology. Radiation dose to specific organs is determined using the Handbook on Organ Doses published by the Bureau of Radiological Health of the Food and Drug Administration; the method is applied to a specific case. In this example dose to an embryo is calculated in examinations involving both fluoroscopy and radiography. In another example dose is determined to a fetus in late pregnancy using tissue air ratios. Patient inquiries about radiation dose are discussed, and some answers are suggested. The reliability of dose calculations is examined.

The Utility of Proton Beam Therapy with Concurrent Chemotherapy for the Treatment of Esophageal Cancers

PubMed Central

Lin, Steven H.

2011-01-01

The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the quality of the radiation delivery is critical for the treatment of esophageal cancer since the esophagus is positioned close to vital structures, such as the heart and lung. The volume and relative doses to these normal tissues affect acute and late term complications. Advances in radiation delivery from 2D to 3D conformal radiation therapy, to Intensity Modulated Radiation Therapy (IMRT) or charged particle therapy (carbon ion or proton beam therapy (PBT)), allow incremental improvements in the therapeutic ratio. This could have implications in non-cancer related morbidity for long term survivors. This article reviews the evolution in radiation technologies and the use of PBT with chemotherapy in the management of esophageal cancer. PMID:24213126

Probing the Production of Extreme-ultraviolet Late-phase Solar Flares Using the Model Enthalpy-based Thermal Evolution of Loops

NASA Astrophysics Data System (ADS)

Dai, Yu; Ding, Mingde

2018-04-01

Recent observations in extreme-ultraviolet (EUV) wavelengths reveal an EUV late phase in some solar flares that is characterized by a second peak in warm coronal emissions (∼3 MK) several tens of minutes to a few hours after the soft X-ray (SXR) peak. Using the model enthalpy-based thermal evolution of loops (EBTEL), we numerically probe the production of EUV late-phase solar flares. Starting from two main mechanisms of producing the EUV late phase, i.e., long-lasting cooling and secondary heating, we carry out two groups of numerical experiments to study the effects of these two processes on the emission characteristics in late-phase loops. In either of the two processes an EUV late-phase solar flare that conforms to the observational criteria can be numerically synthesized. However, the underlying hydrodynamic and thermodynamic evolutions in late-phase loops are different between the two synthetic flare cases. The late-phase peak due to a long-lasting cooling process always occurs during the radiative cooling phase, while that powered by a secondary heating is more likely to take place in the conductive cooling phase. We then propose a new method for diagnosing the two mechanisms based on the shape of EUV late-phase light curves. Moreover, from the partition of energy input, we discuss why most solar flares are not EUV late flares. Finally, by addressing some other factors that may potentially affect the loop emissions, we also discuss why the EUV late phase is mainly observed in warm coronal emissions.

Clinical Outcomes of Image Guided Adaptive Hypofractionated Weekly Radiation Therapy for Bladder Cancer in Patients Unsuitable for Radical Treatment

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

Hafeez, Shaista, E-mail: shaista.hafeez@icr.ac.uk; The Royal Marsden NHS Foundation Trust, Sutton, Surrey; McDonald, Fiona

Purpose and Objectives: We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. Methods and Materials: Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A “plan of the day” radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity was assessed weekly during radiation therapy, at 6 and 12 weeks using the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was assessed at 6 months and 12 monthsmore » using Radiation Therapy Oncology Group grading. Cystoscopy was used to assess local control at 3 months. Cumulative incidence function was used to determine local progression at 1 at 2 years. Death without local progression was treated as a competing risk. Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 86 years (range, 68-97 years). Eighty-seven percent of patients completed their prescribed course of radiation therapy. Genitourinary and gastrointestinal grade 3 acute toxicity was seen in 18% (10/55) and 4% (2/55) of patients, respectively. No grade 4 genitourinary or gastrointestinal toxicity was seen. Grade ≥3 late toxicity (any) at 6 and 12 months was seen in 6.5% (2/31) and 4.3% (1/23) of patients, respectively. Local control after radiation therapy was 92% of assessed patients (60% total population). Cumulative incidence of local progression at 1 year and 2 years for all patients was 7% (95% confidence interval [CI] 2%-17%) and 17% (95% CI 8%-29%), respectively. Overall survival at 1 year was 63% (95% CI 48%-74%). Conclusion: Hypofractionated radiation therapy delivered weekly with a plan of the day approach offers good local control with acceptable toxicity in a patient population not suitable for radical bladder treatment.« less

Predicted Rate of Secondary Malignancies Following Adjuvant Proton Versus Photon Radiation Therapy for Thymoma.

PubMed

Vogel, J; Lin, L; Litzky, L A; Berman, A T; Simone, C B

2017-10-01

Thymic malignancies are the most common tumors of the anterior mediastinum. The benefit of adjuvant radiation therapy for stage II disease remains controversial, and patients treated with adjuvant radiation therapy are at risk of late complications, including radiation-induced secondary malignant neoplasms (SMNs), that may reduce the overall benefit of treatment. We assess the risk of predicted SMNs following adjuvant proton radiation therapy compared with photon radiation therapy after resection of stage II thymic malignancies to determine whether proton therapy improves the risk-benefit ratio. Ten consecutive patients treated with double-scattered proton beam radiation therapy (DS-PBT) were prospectively enrolled in an institutional review board-approved proton registry study. All patients were treated with DS-PBT. Intensity modulated radiation therapy (IMRT) plans for comparison were generated. SMN risk was calculated based on organ equivalent dose. Patients had a median age of 65 years (range, 25-77 years), and 60% were men. All patients had stage II disease, and many had close or positive margins (60%). The median dose was 50.4 Gy (range, 50.4-54.0 Gy) in 1.8-Gy relative biological effectiveness daily fractions. No differences in target coverage were seen with DS-PBT compared with IMRT plans. Significant reductions were seen in mean and volumetric lung, heart, and esophageal doses with DS-PBT compared with IMRT plans (all P≤.01). Significant reductions in SMNs in the lung, breast, esophagus, skin, and stomach were seen with DS-PBT compared with IMRT. For patients with thymoma diagnosed at the median national age, 5 excess secondary malignancies per 100 patients would be avoided by treating them with protons instead of photons. Treatment with proton therapy can achieve comparable target coverage but significantly reduced doses to critical normal structures, which can lead to fewer predicted SMNs compared with IMRT. By decreasing expected late complications, proton therapy may improve the therapeutic ratio of adjuvant radiation therapy for patients with stage II thymic malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

PubMed

Tyran, Marguerite; Gonzague, Laurence; Bouabdallah, Reda; Resbeut, Michel

2014-01-01

Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it's rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy.

Radiation pressure driving of a dusty atmosphere

NASA Astrophysics Data System (ADS)

Tsang, Benny T.-H.; Milosavljević, Miloš

2015-10-01

Radiation pressure can be dynamically important in star-forming environments such as ultra-luminous infrared and submillimetre galaxies. Whether and how radiation drives turbulence and bulk outflows in star formation sites is still unclear. The uncertainty in part reflects the limitations of direct numerical schemes that are currently used to simulate radiation transfer and radiation-gas coupling. An idealized setup in which radiation is introduced at the base of a dusty atmosphere in a gravitational field has recently become the standard test for radiation-hydrodynamics methods in the context of star formation. To a series of treatments featuring the flux-limited diffusion approximation as well as a short-characteristics tracing and M1 closure for the variable Eddington tensor approximation, we here add another treatment that is based on the implicit Monte Carlo radiation transfer scheme. Consistent with all previous treatments, the atmosphere undergoes Rayleigh-Taylor instability and readjusts to a near-Eddington-limited state. We detect late-time net acceleration in which the turbulent velocity dispersion matches that reported previously with the short-characteristics-based radiation transport closure, the most accurate of the three preceding treatments. Our technical result demonstrates the importance of accurate radiation transfer in simulations of radiative feedback.

A Prospective Study of Proton Beam Reirradiation for Esophageal Cancer.

PubMed

Fernandes, Annemarie; Berman, Abigail T; Mick, Rosemarie; Both, Stefan; Lelionis, Kristi; Lukens, John N; Ben-Josef, Edgar; Metz, James M; Plastaras, John P

2016-05-01

Reirradiation to the esophagus carries a significant risk of complications. Proton therapy may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of previously radiated normal tissues. Between June 2010 and February 2014, 14 patients with a history of thoracic radiation and newly diagnosed or locally recurrent esophageal cancer began proton beam reirradiation on a prospective trial. Primary endpoints were feasibility and acute toxicity. Toxicity was graded according Common Toxicity Criteria version 4.0. The median follow-up was 10 months (2-25 months) from the start of reirradiation. Eleven patients received concurrent chemotherapy. The median interval between radiation courses was 32 months (10-307 months). The median reirradiation prescription dose was 54.0 Gy (relative biological effectiveness [RBE]) (50.4-61.2 Gy[RBE]), and the median cumulative prescription dose was 109.8 Gy (76-129.4 Gy). Of the 10 patients who presented with symptomatic disease, 4 patients had complete resolution of symptoms, and 4 had diminished or stable symptoms. Two patients had progressive symptoms. The median time to symptom recurrence was 10 months. Maximum acute nonhematologic toxicity attributable to radiation was grade 2 (64%, N=9), 3 (29%, N=4), 4 (0%), and 5 (7%, N=1). The acute grade 5 toxicity was an esophagopleural fistula more likely related to tumor progression than radiation. Grade 3 nonhematologic acute toxicities included dysphagia, dehydration, and pneumonia. There was 1 late grade 5 esophageal ulcer more likely related to tumor progression than radiation. There were 4 late grade 3 toxicities: heart failure, esophageal stenosis requiring dilation, esophageal ulceration from tumor, and percutaneous endoscopic gastrostomy tube dependence. The median time to local failure was 10 months, and the median overall survival was 14 months. Our data demonstrate that proton reirradiation is feasible, with an encouraging symptom control rate, modest radiation-related toxicity, and favorable survival in this high-risk population. Copyright © 2016 Elsevier Inc. All rights reserved.

Total-Body Irradiation Produces Late Degenerative Joint Damage in Rats

PubMed Central

Hutchinson, Ian D.; Olson, John; Lindburg, Carl A.; Payne, Valerie; Collins, Boyce; Smith, Thomas L.; Munley, Michael T.; Wheeler, Kenneth T.; Willey, Jeffrey S.

2014-01-01

Purpose Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. Materials and Methods 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV x-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. Results T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. Conclusions Late degenerative changes in articular cartilage and bone were observed after total body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage. PMID:24885745

Optical and ultraviolet spectroscopic analysis of SN 2011fe at late times

NASA Astrophysics Data System (ADS)

Friesen, Brian; Baron, E.; Parrent, Jerod T.; Thomas, R. C.; Branch, David; Nugent, Peter E.; Hauschildt, Peter H.; Foley, Ryan J.; Wright, Darryl E.; Pan, Yen-Chen; Filippenko, Alexei V.; Clubb, Kelsey I.; Silverman, Jeffrey M.; Maeda, Keiichi; Shivvers, Isaac; Kelly, Patrick L.; Cohen, Daniel P.; Rest, Armin; Kasen, Daniel

2017-05-01

We present optical spectra of the nearby Type Ia supernova SN 2011fe at 100, 205, 311, 349 and 578 d post-maximum light, as well as an ultraviolet (UV) spectrum obtained with the Hubble Space Telescope at 360 d post-maximum light. We compare these observations with synthetic spectra produced with the radiative transfer code phoenix. The day +100 spectrum can be well fitted with models that neglect collisional and radiative data for forbidden lines. Curiously, including these data and recomputing the fit yields a quite similar spectrum, but with different combinations of lines forming some of the stronger features. At day +205 and later epochs, forbidden lines dominate much of the optical spectrum formation; however, our results indicate that recombination, not collisional excitation, is the most influential physical process driving spectrum formation at these late times. Consequently, our synthetic optical and UV spectra at all epochs presented here are formed almost exclusively through recombination-driven fluorescence. Furthermore, our models suggest that the UV spectrum even as late as day +360 is optically thick and consists of permitted lines from several iron-peak species. These results indicate that the transition to the 'nebular' phase in Type Ia supernovae is complex and highly wavelength dependent.

Optical and ultraviolet spectroscopic analysis of SN 2011fe at late times

DOE PAGES

Friesen, Brian; Baron, E.; Parrent, Jerod T.; ...

2017-02-27

This paper presents optical spectra of the nearby Type Ia supernova SN 2011fe at 100, 205, 311, 349 and 578 d post-maximum light, as well as an ultraviolet (UV) spectrum obtained with the Hubble Space Telescope at 360 d post-maximum light. We compare these observations with synthetic spectra produced with the radiative transfer code PHOENIX. The day +100 spectrum can be well fitted with models that neglect collisional and radiative data for forbidden lines. Curiously, including these data and recomputing the fit yields a quite similar spectrum, but with different combinations of lines forming some of the stronger features. Atmore » day +205 and later epochs, forbidden lines dominate much of the optical spectrum formation; however, our results indicate that recombination, not collisional excitation, is the most influential physical process driving spectrum formation at these late times. Consequently, our synthetic optical and UV spectra at all epochs presented here are formed almost exclusively through recombinationdriven fluorescence. Furthermore, our models suggest that the UV spectrum even as late as day +360 is optically thick and consists of permitted lines from several iron-peak species. These results indicate that the transition to the 'nebular' phase in Type Ia supernovae is complex and highly wavelength dependent.« less

NF-kB activation and its downstream target genes expression after heavy ions exposure

NASA Astrophysics Data System (ADS)

Chishti, Arif Ali; Baumstark-Khan, Christa; Hellweg, Christine; Schmitz, Claudia; Koch, Kristina; Feles, Sebastian

2016-07-01

To enable long-term human space flight cellular radiation response to densely ionizing radiation needs to be better understood for developing appropriate countermeasures to mitigate acute effects and late radiation risks for the astronaut. The biological effectiveness of accelerated heavy ions (which constitute the most important radiation type in space) with high linear energy transfer (LET) for effecting DNA damage response pathways as a gateway to cell death or survival is of major concern not only for space missions but also for new regimes of tumor radiotherapy. In the current research study, the contribution of NF-κB in response to space-relevant radiation qualities was determined by a NF-κB reporter cell line (HEK-pNF-κB-d2EGFP/Neo L2). The NF-κB dependent reporter gene expression (d2EGFP) after ionizing radiation (X-rays and heavy ions) exposure was evaluated by flow cytometry. Because of differences in the extent of NF-κB activation after X-irradiation and heavy ions exposure, it was expected that radiation quality (LET) might play an important role in the cellular radiation response. In addition, the biological effectiveness (RBE) of NF-κB activation and reduction of cellular survival was examined for heavy ions having a broad range of LET (˜0.3 - 9674 keV/µm). Furthermore, the effect of LET on NF-κB target gene expression was analyzed by real time reverse transcriptase quantitative PCR (RT-qPCR). In this study it was proven that NF-κB activation and NF-κB dependent gene expression comprises an early step in cellular radiation response. Taken together, this study clearly demonstrates that NF-κB activation and NF-κB-dependent gene expression by heavy ions are highest in the LET range of ˜50-200 keV/μupm. The up-regulated chemokines and cytokines (CXCL1, CXCL2, CXCL10, IL-8 and TNF) might be important for cell-cell communication among hit as well as unhit cells (bystander effect). The results obtained suggest the NF-κB pathway to be a promising target for pharmacological modulation of cellular radiation response either to improve tumor cell killing during radiotherapy with heavy ions or to mitigate radiation late effects in astronauts or irradiated healthy tissue.

Ion-kill dosimetry

NASA Technical Reports Server (NTRS)

Katz, R.; Cucinotta, F. A.; Fromm, M.; Chambaudet, A.

2001-01-01

Unanticipated late effects in neutron and heavy ion therapy, not attributable to overdose, imply a qualitative difference between low and high LET therapy. We identify that difference as 'ion kill', associated with the spectrum of z/beta in the radiation field, whose measurement we label 'ion-kill dosimetry'.

[Late adverse events after concurrent chemoradiation therapy in long-term survivors with non-small cell lung cancer].

PubMed

Hasegawa, Takaaki; Sawa, Toshiyuki; Futamura, Yohei; Horiba, Akane; Ishiguro, Takashi; Yoshida, Tsutomu; Iida, Takayoshi; Marui, Tsutomu

2013-11-01

Long-term survival in patients with non-small cell lung cancer( NSCLC) can be achieved more frequently with combined modality therapy. However, an increased risk of late treatment-related toxicities has been reported for this treatment strategy. We retrospectively evaluated NSCLC patients treated with chemoradiation therapy from January 1988 to January 2007. Patients who had survived for more than 5 years after treatment were included in an analysis of late adverse events (excluding radiation pneumonitis and pulmonary fibrosis). A total of 188 NSCLC patients treated with chemoradiation therapy were evaluated, with 25 patients having survived for more than 5 years. Of these patients, 4 had stage I disease, 4 had stage IIB disease, 1 had stage IIIA disease, 14 had stage IIIB disease, 1 had stage IV disease, and 1 had disease of unknown stage. The following grade 3 late adverse events were noted: skin ulceration( n=1), skin induration( n=1), brachial plexopathy( n=1), malignant neoplasm( n=1). Adequate management of late adverse events due to chemoradiation therapy is needed for long-term NSCLC survivors.

RADIOPATHIES IN THE HAND OF THE SURGEON

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

Marino, H.

1962-03-01

Several cases are described in which severe radiation injuries occurred in the hands of surgeons during operative procedures requiring fluoroscopy. The radiation lesions appeared to be aggravated by the various mechanical traumas accompanying washing-up processes preceding surgery including brushing the fingers, use of strong disinfectants and detergents, and sprinkling the hands with talcum before donning rubber gloves. These routine measures may cause acute eruptions of old radiation lesions. Various phases in the development of radiation burns on the hands, from the initial dermatitis to the late necrotic changes, are discussed. Fraquently, the early lesions are erroneously diagnosed as allergic eczemamore » so that effective therapeutic measures may not be instituted soon enough. Plastic surgical rapairs of finger lesions, in the cases described, are illustrated. (H.H.D.)« less

Spherically symmetric cosmological spacetimes with dust and radiation — numerical implementation

NASA Astrophysics Data System (ADS)

Lim, Woei Chet; Regis, Marco; Clarkson, Chris

2013-10-01

We present new numerical cosmological solutions of the Einstein Field Equations. The spacetime is spherically symmetric with a source of dust and radiation approximated as a perfect fluid. The dust and radiation are necessarily non-comoving due to the inhomogeneity of the spacetime. Such a model can be used to investigate non-linear general relativistic effects present during decoupling or big-bang nucleosynthesis, as well as for investigating void models of dark energy with isocurvature degrees of freedom. We describe the full evolution of the spacetime as well as the redshift and luminosity distance for a central observer. After demonstrating accuracy of the code, we consider a few example models, and demonstrate the sensitivity of the late time model to the degree of inhomogeneity of the initial radiation contrast.

Current status of radiological protection at nuclear power stations in Japan.

PubMed

Suzuki, Akira; Hori, Shunsuke

2011-07-01

The radiation dose to workers at nuclear power stations (NPSs) in Japan was drastically reduced between the late-1970s and the early-1990s by continuous dose-reduction programmes. The total collective dose of radiation workers in FY 2008 was 84.04 person Sv, while the average collective dose was 1.5 person Sv per reactor. The average annual individual dose was 1.1 mSv and the maximum annual individual dose was 19.5 mSv. These values are sufficiently lower than the regulatory dose limits. Radioactive effluent released from NPSs is already so trivial that additional protective measures will not be necessary. Experience in radiation protection at NPSs has been accumulated over 40 y and will be very useful in establishing a rational radiation control system in the future.

[Brain metastases: Focal treatment (surgery and radiation therapy) and cognitive consequences].

PubMed

Reygagne, Emmanuelle; Du Boisgueheneuc, Foucaud; Berger, Antoine

2017-04-01

Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status and estimated prognostic (DS GPA). Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies (radiation therapy and surgery) with their neuro-cognitive consequences for brain metastases patients and future concerning preservation of cognitive functions. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Efficacy and safety of mesalamine 1 g HS versus 500 mg BID suppositories in mild to moderate ulcerative proctitis: a multicenter randomized study.

PubMed

Lamet, Mark; Ptak, Theodore; Dallaire, Chrystian; Shah, Umed; Grace, Michael; Spenard, Jean; de Montigny, Danielle

2005-07-01

Ulcerative proctitis (UP) usually presents as fresh rectal bleeding. Successful treatment using topical mesalamine 5-aminosalicyclic acid (5-ASA) 500 mg BID suppository led to developing a once-a-day formulation that could contribute to better acceptability and ease of use by patients. The objective of this randomized trial, conducted in 18 centers, was to compare efficacy of 2 modes of treatment with 5-ASA suppositories. Ninety-nine patients with mild or moderate UP limited to 15 cm of the anal margin, evidenced by a disease activity index (DAI) between 4 and 11, were randomized to 5-ASA 500 mg suppository (Canasa; Axcan Pharma) BID or 1 g at bedtime (HS) for 6 weeks. The study used a noninferiority hypothesis based on the mean difference in DAI values after 6 weeks of treatment on an intent-to-treat basis using analysis of covariance. DAI was derived from a composite of the measures of stool frequency, rectal bleeding, mucosal visualization at endoscopy, and general well being. There was no difference between groups at baseline for demographic and clinical parameters. Mean DAIs fell from 6.6 +/- 1.5 (SD) to 1.6 +/- 2.3 in the 500 mg BID group (n = 48) and from 6.1 +/- 1.5 to 1.3 +/- 2.2 in the 1 g HS group (n = 39). There was no significant difference (P = 0.74) in mean DAI at week 6 between the 2 groups. Both groups showed a significant reduction (P < 0.0001) in DAI over the course of the 6 weeks. Both formulations showed effectiveness in reducing each individual component of the DAI. There was no significant difference between treatments in adverse events, and both groups had an overall drug compliance of greater than 95%. This study showed that 1 g HS and 500 mg BID mesalamine suppository treatments of UP patients were equivalent in all facets of efficacy, safety, and compliance in a 6-week trial.

A multicenter, randomized study to evaluate the efficacy and safety of mesalamine suppositories 1 g at bedtime and 500 mg Twice daily in patients with active mild-to-moderate ulcerative proctitis.

PubMed

Lamet, Mark

2011-02-01

Ulcerative proctitis (UP) is a prevalent condition associated with increased morbidity and mortality. Topical mesalamine (5-aminosalicylic acid [5-ASA]) inhibits inflammatory processes in UP. We evaluated effects of mesalamine 1-g suppository administered QHS compared with 500-mg suppository administered BID on UP activity (e.g., disease extension/mucosal appearance), remission, onset of response, safety and compliance in 97 patients with UP. A 6-week, randomized, multicenter, parallel-group, noninferiority study was conducted (and published) with Disease Activity Index (DAI) at week 6 as the primary efficacy variable and individual components of DAI at week 6 (i.e., stool frequency, rectal bleeding, mucosal appearance, global assessment) as secondary variables. Unreported outcomes were remission (DAI < 3 at weeks 3 and 6), disease extension, and complete response to treatment (DAI = 0; post-hoc, exploratory analysis). DAI values after 6 weeks were significantly reduced (±SD) from 6.6 ± 1.5 to 1.6 ± 2.3 (500-mg BID); and from 6.1 ± 1.5 to 1.3 ± 2.2 (1-g QHS). Mucosal appearance significantly improved from baseline after 3 and 6 weeks of treatment from 1.8 ± 0.5 to 0.8 ± 0.7 and 0.5 ± 0.7 (500-mg BID; P ≤ 0.0062) and from 1.7 ± 0.5 to 0.9 ± 0.5 and 0.4 ± 0.6 (1-g QHS; P ≤ 0.0001), respectively. Remission was comparable (78.3-86.1%); onset of response generally occurred within 3 weeks, and disease extension was reduced (>70%) after 6 weeks in both groups. Mesalamine was well tolerated. Compliance was >96%. Mesalamine 500-mg BID and 1-g QHS suppositories are safe and effective for patients with UP. Most patients reported significant improvement within 3 weeks and UP remission and reduced disease extension after 6 weeks of treatment. Validity of QHS administration was confirmed.

Public health activities for mitigation of radiation exposures and risk communication challenges after the Fukushima nuclear accident

PubMed Central

Shimura, Tsutomu; Yamaguchi, Ichiro; Terada, Hiroshi; Robert Svendsen, Erik; Kunugita, Naoki

2015-01-01

Herein we summarize the public health actions taken to mitigate exposure of the public to radiation after the Fukushima accident that occurred on 11 March 2011 in order to record valuable lessons learned for disaster preparedness. Evacuations from the radiation-affected areas and control of the distribution of various food products contributed to the reduction of external and internal radiation exposure resulting from the Fukushima incident. However, risk communication is also an important issue during the emergency response effort and subsequent phases of dealiing with a nuclear disaster. To assist with their healing process, sound, reliable scientific information should continue to be disseminated to the radiation-affected communities via two-way communication. We will describe the essential public health actions following a nuclear disaster for the early, intermediate and late phases that will be useful for radiological preparedness planning in response to other nuclear or radiological disasters. PMID:25862700

Cataract after exposure to non-ionizing radiant energy.

PubMed Central

Zaret, M M; Snyder, W Z; Birenbaum, L

1976-01-01

The case histories of two individuals exposed to thermal radiation emitted from an electric oven and range were presented. In one patient, earlier exposure to medical diathermy appears to have initiated delayed or late-appearing, capsular cataracts. Instead of the anticipated slow progression, the cataractogenesis was accelerated following recent, repeated exposure to the intense, infrared radiation. In the other patient, exposed solely to infrared radiation, a chorioretinal lesion indistinguishable from the type characteristically secondary to repeated, thermal radiation was observed. More recently, the earliest sign of thermal radiation cataractogenesis, capsular opacification, has become evident. The widespread availability of radiant energy sources such as diathermy machines, microwave ovens, and electric ovens and ranges makes it imperative to examine carefully any possible hazards that may result from their use. With this in mind, radiant energy should be considered in the differential diagnosis of cataractogenesis. Images PMID:990233

Observing the earth radiation budget from satellites - Past, present, and a look to the future

NASA Technical Reports Server (NTRS)

House, F. B.

1985-01-01

Satellite measurements of the radiative exchange between the planet earth and space have been the objective of many experiments since the beginning of the space age in the late 1950's. The on-going mission of the Earth Radiation Budget (ERB) experiments has been and will be to consider flight hardware, data handling and scientific analysis methods in a single design strategy. Research and development on observational data has produced an analysis model of errors associated with ERB measurement systems on polar satellites. Results show that the variability of reflected solar radiation from changing meteorology dominates measurement uncertainties. As an application, model calculations demonstrate that measurement requirements for the verification of climate models may be satisfied with observations from one polar satellite, provided there is information on diurnal variations of the radiation budget from the ERBE mission.

Ionizing Radiation as an Industrial Health Problem

PubMed Central

Trewin, R. B.

1964-01-01

Ionizing radiation, first as x-rays, later in natural form, was discovered in Europe in the late 1890's. Immediate practical uses were found for these discoveries, particularly in medicine. Unfortunately, because of the crude early equipment and ignorance of the harmful effects of radiation, many people were injured, some fatally. Because of these experiences, committees and regulatory bodies were set up to study the problem. These have built up an impressive fund of knowledge useful in radiation protection. With the recent development of the peaceful uses of atomic energy, sources of radioactivity have appeared cheaply and in abundance. A rapidly growing number are finding industrial application. Because of their potential risk to humans, the industrial physician must acquire new knowledge and skills so that he may give proper guidance in this new realm of preventive medicine. The Radiation Protection Program of one such industry, the Hydro-Electric Power Commission of Ontario, is summarized. PMID:14105012

New measurements for hadrontherapy and space radiation: biology

NASA Technical Reports Server (NTRS)

Blakely, E. A.

2001-01-01

The dual goals of optimizing clinical efficacy of hadrontherapy and determining radiation risk estimates for space research have intersected to a common focus for investigation of the biological effects of charged particles. This paper briefly highlights recent international progress at accelerator facilities engaged in both biological and clinical studies of the effects of particle beams, primarily protons, carbon and iron ions. Basic mechanisms of molecular, cellular and tissue responses continue under investigation for radiations with a range of ionization densities. Late normal tissue effects, including the risk of cancer in particular, are of importance for both research fields. International cooperation has enhanced the rate of progress as evidenced by recent publications. Specific areas of biomedical research related to the biological radiotoxicity of critical organs (especially the central nervous system), individual radiosensitivities to radiation carcinogenesis, and the analysis of effects in mixed radiation fields still require more research. Recommendations for addressing these issues are made.

IONIZING RADIATION AS AN INDUSTRIAL HEALTH PROBLEM.

PubMed

TREWIN, R B

1964-01-04

Ionizing radiation, first as x-rays, later in natural form, was discovered in Europe in the late 1890's. Immediate practical uses were found for these discoveries, particularly in medicine. Unfortunately, because of the crude early equipment and ignorance of the harmful effects of radiation, many people were injured, some fatally. Because of these experiences, committees and regulatory bodies were set up to study the problem. These have built up an impressive fund of knowledge useful in radiation protection.With the recent development of the peaceful uses of atomic energy, sources of radioactivity have appeared cheaply and in abundance. A rapidly growing number are finding industrial application. Because of their potential risk to humans, the industrial physician must acquire new knowledge and skills so that he may give proper guidance in this new realm of preventive medicine.The Radiation Protection Program of one such industry, the Hydro-Electric Power Commission of Ontario, is summarized.

Clinical outcome in dogs with nasal tumors treated with intensity-modulated radiation therapy.

PubMed

Hunley, David W; Mauldin, G Neal; Shiomitsu, Keijiro; Mauldin, Glenna E

2010-03-01

Intensity-modulated radiation therapy (IMRT) is a valuable tool in human radiation oncology, but information on its use in veterinary medicine is lacking. In this study, 12 dogs with nasal tumors were treated with IMRT at a median radiation dose of 54 Gy. Patient survival times and frequency and severity of side effects on ocular structures, oral mucosa, and skin were recorded. Eight dogs (67%) had resolution of clinical signs during radiation therapy. Median overall survival time was 446 d with a 50% 1-year and a 25% 2-year survival rate. Minimal grade 2 or 3 acute skin toxicity, no grade 2 or 3 late skin toxicity, and no grade 2 or 3 toxicity to oral mucosa or the eye opposite the tumor were identified in the dogs treated with IMRT in this study. The ipsilateral eye could not be routinely spared due to its proximity to the tumor.

Clinical outcome in dogs with nasal tumors treated with intensity-modulated radiation therapy

PubMed Central

Hunley, David W.; Mauldin, G. Neal; Shiomitsu, Keijiro; Mauldin, Glenna E.

2010-01-01

Intensity-modulated radiation therapy (IMRT) is a valuable tool in human radiation oncology, but information on its use in veterinary medicine is lacking. In this study, 12 dogs with nasal tumors were treated with IMRT at a median radiation dose of 54 Gy. Patient survival times and frequency and severity of side effects on ocular structures, oral mucosa, and skin were recorded. Eight dogs (67%) had resolution of clinical signs during radiation therapy. Median overall survival time was 446 d with a 50% 1-year and a 25% 2-year survival rate. Minimal grade 2 or 3 acute skin toxicity, no grade 2 or 3 late skin toxicity, and no grade 2 or 3 toxicity to oral mucosa or the eye opposite the tumor were identified in the dogs treated with IMRT in this study. The ipsilateral eye could not be routinely spared due to its proximity to the tumor. PMID:20514254

Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT

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

Tol-Geerdink, Julia J. van; Stalmeier, Peep F.M.; Department of Medical Technology Assessment, Radboud University Nijmegen Medical Center, Nijmegen

Purpose: A higher radiation dose is believed to result in a larger probability of tumor control and a higher risk of side effects. To make an evidence-based choice of dose, the relation between dose and outcome needs to be known. This study focuses on the dose-response relation for prostate cancer. Methods and Materials: A systematic review was carried out on the literature from 1990 to 2003. From the selected studies, the radiation dose, the associated 5-year survival, 5-year bNED (biochemical no evidence of disease), acute and late gastrointestinal (GI) and genitourinary (GU) morbidity Grade 2 or more, and sexual dysfunctionmore » were extracted. With logistic regression models, the relation between dose and outcome was described. Results: Thirty-eight studies met our criteria, describing 87 subgroups and involving up to 3000 patients per outcome measure. Between the (equivalent) dose of 70 and 80 Gy, various models estimated an increase in 5-year survival (ranging from 10% to 11%), 5-year bNED for low-risk patients (5-7%), late GI complications (12-16%), late GU complications (8-10%), and erectile dysfunction (19-24%). Only for the overall 5-year bNED, results were inconclusive (range, 0-18%). Conclusions: The data suggest a relationship between dose and outcome measures, including survival. However, the strength of these conclusions is limited by the sometimes small number of studies, the incompleteness of the data, and above all, the correlational nature of the data. Unambiguous proof for the dose-response relationships can, therefore, only be obtained by conducting randomized trials.« less

Exercise programming and counseling preferences of breast cancer survivors during or after radiation therapy.

PubMed

Karvinen, Kristina H; Raedeke, Thomas D; Arastu, Hyder; Allison, Ron R

2011-09-01

To explore exercise programming and counseling preferences and exercise-related beliefs in breast cancer survivors during and after radiation therapy, and to compare differences based on treatment and insurance status. Cross-sectional survey. Ambulatory cancer center in a rural community in eastern North Carolina. 91 breast cancer survivors during or after radiation therapy. The researchers administered the questionnaire to participants. Exercise programming and counseling preferences and exercise beliefs moderated by treatment status (on-treatment, early, and late survivors) and insurance status (Medicaid, non-Medicaid). Chi-square analyses indicated that fewer Medicaid users were physically active and reported health benefits as an advantage of exercise compared to non-Medicaid users (p < 0.05). In addition, more Medicaid users preferred exercise programming at their cancer center compared to non-Medicaid users (p < 0.05). More on-treatment and early survivors listed health benefits as advantages to exercise, but fewer indicated weight control as an advantage compared to late survivors (p < 0.05). Early survivors were more likely than on-treatment survivors to indicate that accessible facilities would make exercising easier for them (p < 0.05). Medicaid users are less active, less likely to identify health benefits as an advantage for exercising, and more likely to prefer cancer center-based exercise programming compared to non-Medicaid users. In addition, on-treatment and early survivors are more likely to list health benefits and less likely to indicate weight control as advantages of exercising compared to late survivors. The low activity levels of Medicaid users may be best targeted by providing cancer center-based exercise programming. Exercise interventions may be most effective if tailored to the unique needs of treatment status.

IL6-174 G>C Polymorphism (rs1800795) Association with Late Effects of Low Dose Radiation Exposure in the Portuguese Tinea Capitis Cohort

PubMed Central

Mendes, Adélia; Costa, Natália Rios; Chora, Inês; Ferreira, Sara; Araújo, Emanuel; Lopes, Pedro; Rosa, Gilberto; Marques, Pedro; Bettencourt, Paulo; Oliveira, Inês; Costa, Francisco; Ramos, Isabel; Teles, Maria José; Guimarães, João Tiago; Sobrinho-Simões, Manuel; Soares, Paula

2016-01-01

Head and neck cancers, and cardiovascular disease have been described as late effects of low dose radiation (LDR) exposure, namely in tinea capitis cohorts. In addition to radiation dose, gender and younger age at exposure, the genetic background might be involved in the susceptibility to LDR late effects. The -174 G>C (rs1800795) SNP in IL6 has been associated with cancer and cardiovascular disease, nevertheless this association is still controversial. We assessed the association of the IL6-174 G>C SNP with LDR effects such as thyroid carcinoma, basal cell carcinoma and carotid atherosclerosis in the Portuguese tinea capitis cohort. The IL6-174 G>C SNP was genotyped in 1269 individuals formerly irradiated for tinea capitis. This sampling group included thyroid cancer (n = 36), basal cell carcinoma (n = 113) and cases without thyroid or basal cell carcinoma (1120). A subgroup was assessed for atherosclerosis by ultrasonography (n = 379) and included matched controls (n = 222). Genotypes were discriminated by real-time PCR using a TaqMan SNP genotyping assay. In the irradiated group, we observed that the CC genotype was significantly associated with carotid plaque risk, both in the genotypic (OR = 3.57, CI = 1.60–7.95, p-value = 0.002) and in the recessive (OR = 3.02, CI = 1.42–6.42, p-value = 0.004) models. Irradiation alone was not a risk factor for carotid atherosclerosis. We did not find a significant association of the IL6-174 C allele with thyroid carcinoma or basal cell carcinoma risk. The IL6-174 CC genotype confers a three-fold risk for carotid atherosclerotic disease suggesting it may represent a genetic susceptibility factor in the LDR context. PMID:27662210

Radiation dose from MDCT using Monte Carlo simulations: estimating fetal dose due to pulmonary embolism scans accounting for overscan

NASA Astrophysics Data System (ADS)

Angel, E.; Wellnitz, C.; Goodsitt, M.; DeMarco, J.; Cagnon, C.; Ghatali, M.; Cody, D.; Stevens, D.; McCollough, C.; Primak, A.; McNitt-Gray, M.

2007-03-01

Pregnant women with shortness of breath are increasingly referred for CT Angiography to rule out Pulmonary Embolism (PE). While this exam is typically focused on the lungs, extending scan boundaries and overscan can add to the irradiated volume and have implications on fetal dose. The purpose of this work was to estimate radiation dose to the fetus when various levels of overscan were encountered. Two voxelized models of pregnant patients derived from actual patient anatomy were created based on image data. The models represent an early (< 7 weeks) and late term pregnancy (36 weeks). A previously validated Monte Carlo model of an MDCT scanner was used that takes into account physical details of the scanner. Simulated helical scans used 120 kVp, 4x5 mm beam collimation, pitch 1, and varying beam-off locations (edge of the irradiated volume) were used to represent different protocols plus overscan. Normalized dose (mGy/100mAs) was calculated for each fetus. For the early term and the late term pregnancy models, fetal dose estimates for a standard thoracic PE exam were estimated to be 0.05 and 0.3 mGy/100mAs, respectively, increasing to 9 mGy/100mAs when the beam-off location was extended to encompass the fetus. When performing PE exams to rule out PE in pregnant patients, the beam-off location may have a large effect on fetal dose, especially for late term pregnancies. Careful consideration of ending location of the x-ray beam - and not the end of image data - could result in significant reduction in radiation dose to the fetus.

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans.

PubMed

Chaikh, Abdulhamid; Calugaru, Valentin; Bondiau, Pierre-Yves; Thariat, Juliette; Balosso, Jacques

2018-06-07

The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. 14 pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < 0.05, using the three NTCP concepts. However, applying the same TD 50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Since estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD 50/5 , a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient's plan.

Evaluation of Planned Treatment Breaks During Radiation Therapy for Anal Cancer: Update of RTOG 92-08

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

Konski, Andre; Garcia, Miguel; John, Madhu

2008-09-01

Purpose: Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study. Methods and Materials: Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure weremore » estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test. Results: Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity. Conclusions: No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts.« less

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

NASA Technical Reports Server (NTRS)

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

Radiation Dose-Volume Effects in the Larynx and Pharynx

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

Rancati, Tiziana; Schwarz, Marco; Allen, Aaron M.

2010-03-01

The dose-volume outcome data for RT-associated laryngeal edema, laryngeal dysfunction, and dysphagia, have only recently been addressed, and are summarized. For late dysphagia, a major issue is accurate definition and uncertainty of the relevant anatomical structures. These and other issues are discussed.

Momentum and energy balance in late-type stellar winds

NASA Technical Reports Server (NTRS)

Macgregor, K. B.

1981-01-01

Observations at ultraviolet and X-ray wavelengths indicate that the classical picture of a static stellar atmosphere containing a radiative equilibrium temperature distribution is inapplicable to the majority of late type stars. Mass loss and the presence of atmospheric regions characterized by gas temperatures in excess of the stellar effective temperature appear to be almost ubiquitous throughout the HR diagram. Evidence pertaining to the thermal and dynamical structure of the outer envelopes of cool stars is summarized. These results are compared with the predictions of several theoretical models which were proposed to account for mass loss from latetype stars. Models in which the outflow is thermally radiatively, or wave driven are considered for identification of the physical processes responsible for the observed wind properties. The observed variation of both the wind, thermal and dynamical structure as one proceeds from the supergiant branch toward the main sequence in the cool portion of the HR diagram give consideration to potential mechanisms for heating and cooling the flow from low gravity stars.

Whole brain radiotherapy for brain metastasis

PubMed Central

McTyre, Emory; Scott, Jacob; Chinnaiyan, Prakash

2013-01-01

Whole brain radiotherapy (WBRT) is a mainstay of treatment in patients with both identifiable brain metastases and prophylaxis for microscopic disease. The use of WBRT has decreased somewhat in recent years due to both advances in radiation technology, allowing for a more localized delivery of radiation, and growing concerns regarding the late toxicity profile associated with WBRT. This has prompted the development of several recent and ongoing prospective studies designed to provide Level I evidence to guide optimal treatment approaches for patients with intracranial metastases. In addition to defining the role of WBRT in patients with brain metastases, identifying methods to improve WBRT is an active area of investigation, and can be classified into two general categories: Those designed to decrease the morbidity of WBRT, primarily by reducing late toxicity, and those designed to improve the efficacy of WBRT. Both of these areas of research show diversity and promise, and it seems feasible that in the near future, the efficacy/toxicity ratio may be improved, allowing for a more diverse clinical application of WBRT. PMID:23717795

46-year-old man with a spinal cord mass.

PubMed

Sanders, Mary Ann; Vitaz, Todd; Rosenblum, Marc; Plaga, Alexis R; Parker, Joseph C; Parker, John R

2011-01-01

Medulloblastoma accounts for only 1% of all adult CNS tumors. Likewise, recurrence of adult medulloblastoma greater than 20 years after initial diagnosis is extremely rare.We describe a case of adult medulloblastoma with late relapse of disease. The patient was 24 years old when first diagnosed and was treated with total tumor resection and craniospinal radiation. At the age of 45, an enhancing 1.3 cm intradural extramedullary spinal cord lesion at T5 was discovered on MRI. This was presumed to be recurrent medulloblastoma in the form of drop metastasis and the patient was treated with spinal radiation. Several months following treatment, at the age of 46, a follow-up MRI demonstrated an enhancing 1.4 cm intradural extramedullary spinal cord lesion at T7. The lesion was resected and histopathologic examination was most consistent with medulloblastoma, late drop metastasis. Although rare, adult medulloblastoma recurring 20 years after initial diagnosis should always be considered in the main differential diagnosis when working up CNS lesions at or outside the primary tumor site.

Consistency of Post-Newtonian Waveforms with Numerical Relativity

NASA Technical Reports Server (NTRS)

Baker, John G.; vanMeter, James R.; McWilliams, Sean T.; Centrella, Joan; Kelly, Bernard J.

2007-01-01

General relativity predicts the gravitational radiation signatures of mergers of compact binaries,such as coalescing binary black hole systems. Derivations of waveform predictions for such systems are required for optimal scientific analysis of observational gravitational wave data, and have so far been achieved primarily with the aid of the post-Newtonian (PN) approximation. The quaIity of this treatment is unclear, however, for the important late inspiral portion. We derive late-inspiral wave forms via a complementary approach, direct numerical simulation of Einstein's equations, which has recently matured sufficiently for such applications. We compare waveform phasing from simulations covering the last approximately 14 cycles of gravitational radiation from an equal-mass binary system of nonspinning black holes with corresponding 3PN and 3.5PN waveforms. We find phasing agreement consistent with internal error estimates based in either approach, at the level of one radian over approximately 10 cycles. The result suggests that PN waveforms for this system are effective roughly until the system reaches its last stable orbit just prior to the final merger.

Consistency of Post-Newtonian Waveforms with Numerical Relativity

NASA Technical Reports Server (NTRS)

Baker, John G.; vanMeter, James R.; McWilliams, Sean T.; Cewntrella, Joan; Kelly, Bernard J.

2006-01-01

General relativity predicts the gravitational radiation signatures of mergers of compact binaries, such as coalescing binary black hole systems. Derivations of waveform predictions for such systems are required for optimal scientific analysis of observational gravitational wave data, and have so far been achieved primarily with the aid of the post-Newtonian (PN) approximation. The quality of this treatment is unclear, however, for the important late inspiral portion. We derive late-inspiral waveforms via a complementary approach, direct numerical simulation of Einstein's equations, which has recently matured sufficiently for such applications. We compare waveform phasing from simulations covering the last approximately 14 cycles of gravitational radiation from an equal-mass binary system of nonspinning black holes with the corresponding 3PN and 3.5PN orbital phasing. We find agreement consistent with internal error estimates based on either approach at the level of one radian over approximately 10 cycles. The result suggests that PN waveforms for this system are effective roughly until the system reaches its last stable orbit just prior to the final merger/

Ionizing Radiation-Induced Immune and Inflammatory Reactions in the Brain

PubMed Central

Lumniczky, Katalin; Szatmári, Tünde; Sáfrány, Géza

2017-01-01

Radiation-induced late brain injury consisting of vascular abnormalities, demyelination, white matter necrosis, and cognitive impairment has been described in patients subjected to cranial radiotherapy for brain tumors. Accumulating evidence suggests that various degrees of cognitive deficit can develop after much lower doses of ionizing radiation, as well. The pathophysiological mechanisms underlying these alterations are not elucidated so far. A permanent deficit in neurogenesis, chronic microvascular alterations, and blood–brain barrier dysfunctionality are considered among the main causative factors. Chronic neuroinflammation and altered immune reactions in the brain, which are inherent complications of brain irradiation, have also been directly implicated in the development of cognitive decline after radiation. This review aims to give a comprehensive overview on radiation-induced immune alterations and inflammatory reactions in the brain and summarizes how these processes can influence cognitive performance. The available data on the risk of low-dose radiation exposure in the development of cognitive impairment and the underlying mechanisms are also discussed. PMID:28529513

Soft-Hair-Enhanced Entanglement Beyond Page Curves in a Black Hole Evaporation Qubit Model

NASA Astrophysics Data System (ADS)

Hotta, Masahiro; Nambu, Yasusada; Yamaguchi, Koji

2018-05-01

We propose a model with multiple qubits that reproduces the thermal properties of four-dimensional Schwarzschild black holes (BHs) by simultaneously taking account of the emission of Hawking particles and the zero-energy soft-hair evaporation at the horizon. The results verify that the entanglement entropy between a qubit and other subsystems, including emitted radiation, is much larger than the BH entropy analogue of the qubit, as opposed to the Page curve prediction. Our result suggests that early Hawking radiation is entangled with soft hair and that late Hawking radiation can be highly entangled with the degrees of freedom of a BH, avoiding the emergence of a firewall at the horizon.

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

Marx, R.E.; Johnson, R.P.

The radiobiology of osteoradionecrosis is a complex of cellular death and cellular functional impairments from radiation energy transfers. Four studies of irradiated patients and a data base from 536 patients with osteoradionecrosis revealed separate pathophysiologic conditions for osteoradionecrosis induced by early trauma, osteoradionecrosis induced by late trauma, and spontaneous osteoradionecrosis. A large body of data suggested useful clinical guidelines for the management of irradiated patients. The guidelines, in part, include a recommendation for deferring radiation treatment for 21 days after tissue wounding, if possible; a relative contraindication to wounding tissue during a radiation course; a recommendation for the use ofmore » hyperbaric oxygen before wounding; and a strong recommendation to provide comprehensive dental care to the irradiated patient.« less

Severe esophageal toxicity after thoracic radiation therapy for lung cancer associated with the human immunodeficiency virus: a case report and review of the literature.

PubMed

Leigh, B R; Lau, D H

1998-10-01

This case report documents severe esophagitis and rapid esophageal stricture formation in a man infected with the human immunodeficiency virus (HIV) who was treated with standard thoracic irradiation for locally advanced non-small-cell lung cancer. Severe late esophageal toxicity is a rare complication of radiation therapy in patients who are HIV negative, but those who are HIV positive may be at increased risk. This article reviews the literature suggesting that HIV infection may lead to unusually severe radiation-induced mucosal injury. High-dose chest irradiation should be performed with caution in this group of patients.

Low Interrater Reliability in Grading of Rectal Bleeding Using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity Scales: A Survey of Radiation Oncologists

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

Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.

2014-12-01

Purpose: To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding. Methods and Materials: From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participantsmore » were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents. Results: Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21). Conclusion: Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both reporting and interpretation.« less

Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

NASA Technical Reports Server (NTRS)

Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

2017-01-01

Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative biological effectiveness (RBE) of radiation are different for different radiation sources, for different cell types, and for the same cell type with different genetic background at different times after radiation exposure. Caution must be taken in using RBE value to estimate biological effects from radiation exposure.

Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

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

Aluwini, Shafak, E-mail: s.aluwini@erasmusmc.nl; Rooij, Peter H.E. van; Kirkels, Wim J.

2014-03-01

Purpose: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). Methods and Materials: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-freemore » survival. The endpoints were constructed according to the Kaplan-Meier method. Results: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. Conclusions: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.« less

The sail-backed reptile Ctenosauriscus from the latest Early Triassic of Germany and the timing and biogeography of the early archosaur radiation.

PubMed

Butler, Richard J; Brusatte, Stephen L; Reich, Mike; Nesbitt, Sterling J; Schoch, Rainer R; Hornung, Jahn J

2011-01-01

Archosaurs (birds, crocodilians and their extinct relatives including dinosaurs) dominated Mesozoic continental ecosystems from the Late Triassic onwards, and still form a major component of modern ecosystems (>10,000 species). The earliest diverse archosaur faunal assemblages are known from the Middle Triassic (c. 244 Ma), implying that the archosaur radiation began in the Early Triassic (252.3-247.2 Ma). Understanding of this radiation is currently limited by the poor early fossil record of the group in terms of skeletal remains. We redescribe the anatomy and stratigraphic position of the type specimen of Ctenosauriscus koeneni (Huene), a sail-backed reptile from the Early Triassic (late Olenekian) Solling Formation of northern Germany that potentially represents the oldest known archosaur. We critically discuss previous biomechanical work on the 'sail' of Ctenosauriscus, which is formed by a series of elongated neural spines. In addition, we describe Ctenosauriscus-like postcranial material from the earliest Middle Triassic (early Anisian) Röt Formation of Waldhaus, southwestern Germany. Finally, we review the spatial and temporal distribution of the earliest archosaur fossils and their implications for understanding the dynamics of the archosaur radiation. Comprehensive numerical phylogenetic analyses demonstrate that both Ctenosauriscus and the Waldhaus taxon are members of a monophyletic grouping of poposauroid archosaurs, Ctenosauriscidae, characterised by greatly elongated neural spines in the posterior cervical to anterior caudal vertebrae. The earliest archosaurs, including Ctenosauriscus, appear in the body fossil record just prior to the Olenekian/Anisian boundary (c. 248 Ma), less than 5 million years after the Permian-Triassic mass extinction. These earliest archosaur assemblages are dominated by ctenosauriscids, which were broadly distributed across northern Pangea and which appear to have been the first global radiation of archosaurs.

Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I trial and intracellular drug incorporation study.

PubMed

Eisbruch, A; Shewach, D S; Bradford, C R; Littles, J F; Teknos, T N; Chepeha, D B; Marentette, L J; Terrell, J E; Hogikyan, N D; Dawson, L A; Urba, S; Wolf, G T; Lawrence, T S

2001-02-01

To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy

PubMed Central

Yoshida, E. J.; Chen, H.; Torres, M. A.; Curran, W. J.; Liu, T.

2011-01-01

Purpose: Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study’s purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy.Methods : Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters—melanin and erythema indices—were used to quantitatively assess skin discoloration. Two ultrasound parameters—skin thickness and Pearson coefficient of the hypodermis—were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores).Results: Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters.Conclusions: Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life. PMID:21992389

Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy.

PubMed

Yoshida, E J; Chen, H; Torres, M A; Curran, W J; Liu, T

2011-10-01

Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy. Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores). Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters. Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life.

Lighting Condition Analysis for Mars' Moon Phobos

NASA Technical Reports Server (NTRS)

Li, Zu Qun; de Carufel, Guy; Crues, Edwin Z.; Bielski, Paul

2016-01-01

This study used high fidelity computer simulation to investigate the lighting conditions, specifically the solar radiation flux over the surface, on Phobos. Ephemeris data from the Jet Propulsion Laboratory (JPL) DE405 model was used to model the state of the Sun, Earth, Moon, and Mars. An occultation model was developed to simulate Phobos' self-shadowing and its solar eclipses by Mars. The propagated Phobos state was compared with data from JPL's Horizon system to ensure the accuracy of the result. Results for Phobos lighting conditions over one Martian year are presented, which include the duration of solar eclipses, average solar radiation intensity, surface exposure time, and radiant exposure for both sun tracking and fixed solar arrays. The results show that: Phobos' solar eclipse time varies throughout the Martian year, with longer eclipse durations during the Martian northern spring and fall seasons and no eclipses during the Martian northern summer and winter seasons; solar radiation intensity is close to minimum in late spring and close to maximum in late fall; exposure time per orbit is relatively constant over the surface during the spring and fall but varies with latitude during the summer and winter; and Sun tracking solar arrays generate more energy than a fixed solar array. A usage example of the result is also present in this paper to demonstrate the utility.

Low-energy particle experiments - electron analyzer (LEPe) for the Arase mission

NASA Astrophysics Data System (ADS)

Chang, T. F.; Kazama, Y.; Wang, B. J.; Wang, S. Y.; Chiang, C. Y.; Tam, S. W. Y.; Asamura, K.

2017-12-01

Academia Sinica Institute of Astronomy and Astrophysics (ASIAA) and Institute of Space and Plasma Sciences (ISAPS) at National Cheng Kung University in Taiwan developed a low-energy electron instrument (LEPe) for the Exploration of Energization and Radiation in Geospace (ERG) mission, in collaboration with Institute of Space and Astronautical Science (ISAS), Japan. The LEPe instrument employs a toroidal tophat-type electrostatic analyzer with multi-channel plates, and measures electrons with energies of 20 eV to 19 keV. The analyzer was designed toward relatively large sensitivity for statistically better signals. Against background radiations, the analyzer has 6mm thick aluminum shields and one background anode for reduction and subtraction of radiation signals. The instrument measures three dimensional electron fluxes in approximately 8 seconds of one spin, with angular resolutions of 22.5 degrees. For the purpose of resolving loss cones, specific 45 degrees are divided into 12 channels, 3.75 degrees for each. The ERG spacecraft was successfully launched late in 2016, and science operations phase has started since late March, 2017. The LEPe instrument is functioning well and is measuring low-energy electrons that dominate in the inner magnetosphere and also control wave activities. In this presentation, we will explain the LEPe instrument onboard the ERG spacecraft and will introduce initial results of the measurements.

Massive bleeding from the ileum: a late complication of pelvic radiotherapy

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

Taverner, D.; Talbot, I.C.; Carr-Locke, D.L.

1982-01-01

Recurrent massive hemorrhage from the ileum as a late complication of radiotherapy has not previously been documented. We describe two patients with a history of pelvic radiotherapy 18 months and 11 yr before, in whom the source of melena was localized to the small bowel preoperatively. Characteristic serosal appearances of ileal radiation injury were present at laparotomy and resection of the terminal ileum controlled the hemorrhage. Pathological study revealed no ulceration but multiple telangiectatic vessels in the tips of mucosal villi. This cause should be considered in patients with obscure gastrointestinal bleeding previously exposed to pelvic radiotherapy.

Increase in sexually transmitted infections in a cohort of outpatient HIV-positive men who have sex with men in the Parisian region.

PubMed

Farfour, E; Dimi, S; Majerholc, C; Fourn, E; Séné, T; Chaida, M B; Vasse, M; Zucman, D

2017-11-01

To describe the increased incidence of sexually transmitted infections (STIs) in a cohort of HIV-infected men who have sex with men (MSM), followed in a tertiary hospital of the Île-de-France region. We performed a monocentric, retrospective, and prospective study. We included symptomatic HIV-infected MSM patients who consulted for their annual consultation. One hundred and eighty patients were seen between 2008-2011 and 215 between 2012-2015. We observed an increased incidence of STIs between the two periods (14 and 29.3%, respectively). These STIs includes: syphilis, hepatitis C, urethritis, and proctitis due to Chlamydia trachomatis and Neisseria gonorrhea. A better management of symptomatic and asymptomatic STIs is needed for HIV-infected MSM patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The rise and fall of late Paleozoic trilobites of the United States

USGS Publications Warehouse

Brezinski, D.K.

1999-01-01

Based on range data and generic composition, four stages of evolution are recognized for late Paleozoic trilobites of the contiguous United States. Stage 1 occurs in the Lower Mississippian (Kinderhookian-Osagean) and is characterized by a generically diverse association of short-ranging, stenotopic species that are strongly provincial. Stage 2 species are present in the Upper Mississippian and consist of a single, eurytopic, pandemic genus, Paladin. Species of Stage 2 are much longer-ranging than those of Stage 1, and some species may have persisted for as long as 12 m.y. Stage 3 is present within Pennsylvanian and Lower Permian strata and consists initially of the eurytopic, endemic genera Sevillia and Ameura as well as the pandemic genus Ditomopyge. During the middle Pennsylvanian the very long-ranging species Ameura missouriensis and Ditomopyge scitula survived for more than 20 m.y. During the late Pennsylvanian and early Permian, a number of pandemic genera appear to have immigrated into what is now North America. Stage 4 is restricted to the Upper Permian (late Leonardian-Guadalupian) strata and is characterized by short-ranging, stenotopic, provincial genera. The main causal factor controlling the four-stage evolution of late Paleozoic trilobites of the United States is interpreted to be eustacy. Whereas Stage 1 represents an adaptive radiation developed during the Lower Mississippian inundation of North America by the Kaskaskia Sequence, Stage 2 is present in strata deposited during the regression of the Kaskaskia sea. Stage 3 was formed during the transgression and stillstand of the Absaroka Sequence and, although initially endemic, Stage 3 faunas are strongly pandemic in the end when oceanic circulation patterns were at a maximum. A mid-Leonardian sea-level drop caused the extinction of Stage 3 fauna. Sea-level rise near the end of the Leonardian and into the Guadalupian created an adaptive radiation of stentopic species of Stage 4 that quickly became extinct with the latest Permian regression.

Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes

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

Romesser, Paul B.; Cahlon, Oren; ProCure Proton Therapy Center, Somerset, New Jersey

Purpose: Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. Methods and Materials: A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicitiesmore » were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom–from–distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. Results: Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom–from–distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. Conclusions: Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.« less

Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives

PubMed Central

Serrano, Nicholas A; Kalman, Noah S; Anscher, Mitchell S

2017-01-01

Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity. PMID:28814898

Public health activities for mitigation of radiation exposures and risk communication challenges after the Fukushima nuclear accident.

PubMed

Shimura, Tsutomu; Yamaguchi, Ichiro; Terada, Hiroshi; Robert Svendsen, Erik; Kunugita, Naoki

2015-05-01

Herein we summarize the public health actions taken to mitigate exposure of the public to radiation after the Fukushima accident that occurred on 11 March 2011 in order to record valuable lessons learned for disaster preparedness. Evacuations from the radiation-affected areas and control of the distribution of various food products contributed to the reduction of external and internal radiation exposure resulting from the Fukushima incident. However, risk communication is also an important issue during the emergency response effort and subsequent phases of dealiing with a nuclear disaster. To assist with their healing process, sound, reliable scientific information should continue to be disseminated to the radiation-affected communities via two-way communication. We will describe the essential public health actions following a nuclear disaster for the early, intermediate and late phases that will be useful for radiological preparedness planning in response to other nuclear or radiological disasters. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Advances in radiation mutagenesis through studies on Drosophila

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

Muller, H. J.

The approximately linear relation between radiation dose and induced lethals, known for Drosophila spermatozoa, is now extended to spermatids. Data are included regarding oogonia. The linearity principle has been confirmed for minute structural changes in spermatozoa. The dependence of gross structural changes, as multi-hit events, on about the 1.5 power of the dose, long known for spermatozoa, is now extended to spermatids and late oocytes, for relatively short exposures. However, these stages unlike spermatozoa are found to allow union of broken chromosomes. Therefore, the frequencies are lower for more dispersed exposures of these stages, and the precise dose relation variesmore » with the timing. Part of the dominant and even recessive lethals induced in late oocytes follow the same frequency pattern and therefore are multi-hit events. Yet there is a much lower chance after oocytic than spermatozoan irradiation that two broken ends derived from different hits will unite, hence most such unions are nonreciprocal. The following is the order of decreasing radiation mutability of different stages found by ourselves and others: spermatids, spermatozoa in females, spermatozoa 0 to 1 day before ejaculation, earlier spermatozoa, late oocytes, gonia of either sex. Lethal frequencies for these stages range over approximately an order of magnitude, gross structural changes far more widely. Of potential usefulness is our extension of the principle of marked reduction of radiation mutagenesis by anoxia, known for spermatozoa in adult males, to those in pupal males and in females to spermatids and to oocytes. In spermatids this reduction is especially marked but the increase caused by substituting oxygen for air is less marked, perhaps because of enzymatic differences. In contrast, the induction of gross structural changes in oocytes, but not in spermatids, is markedly reduced by oxygen post-treatment; it is increased by dehydration. The efficacy of induction of structural changes by treatment of spermatozoa, whether with radiation or chemical mutagens, is correlated with the conditions of sperm utilization and egg production. Improving our perspective on radiation effects, some 800,000 offspring have been scored for spontaneous visible mutations of 13 specific loci. The average point-mutation rate was 0.5 to 1.0 per locus among 10/sup 5/ germ cells. Most mutations occurred in peri-fertilization stages. All loci studied mutated from one to nine times. Loci mutating oftener spontaneously also gave more radiation mutation, in other studies. Spectra of individual loci prove similar for spontaneous and induced mutation. Studies on back-mutations also showed similarity of spontaneous and radiation mutations. The doubling dose for back-mutations of forked induced in spermatozoa was several hundred roentgens, similar to that for direct point-mutations induced in gonia at diverse loci. Recent analyses of human mutational load lead to mutation-rate estimates like those earlier based on extrapolations from Drosophila, thus supporting the significance for man of the present studies. (auth)« less

Precision radiotherapy for cancer of the pancreas: technique and results. [Photons and electrons

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

Dobelbower, R.R. Jr.; Borgelt, B.B.; Strubler, K.A.

1980-09-01

Forty patients with locally extensive, unresectable adenocarcinoma of the pancreas received precision high dose (PHD) radiation therapy with a 45 MeV betatron. PHD radiotherapy was generally well tolerated. During treatment, only 7 patients experienced significant nausea, vomiting, diarrhea or anorexia. Late gastrointestinal radiation reactions were observed in 7 patients. Twelve patients received adjuvant chemotherapy. The projected survival of patients with unresectable pancreatic cancer treated with PHD radiotherapy is comparable to that of patients with resectable disease operated on for cure. The projected one year survival rate is 49%.

[Mediator processes in the brain structures in the late periods after external and combined exposure to ionizing radiation].

PubMed

Taĭts, M Iu; Dudina, T V; Kandybo, T S; Elkina, A I

1990-01-01

In experiments with mature Wistar male rats it was shown that X-radiation of 12.9 mCi/kg and the combined effect of X-rays and 131I of 6.5 mCi/kg changed the rate of mediator processes in the structures responsible for the hypothalamic function regulation. At remote times (6 months) following irradiation differences were observed in the discoordination of mediator interrelations associated with the peculiarities of the indirect effect of external and combined irradiation implemented via endocrine mechanism system.

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

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

Pollom, Erqi L.; Deng, Lei; Pai, Reetesh K.

2015-07-01

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action ofmore » toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.« less

Modelling radiation damage to ESA's Gaia satellite CCDs

NASA Astrophysics Data System (ADS)

Seabroke, George; Holland, Andrew; Cropper, Mark

2008-07-01

The Gaia satellite is a high-precision astrometry, photometry and spectroscopic ESA cornerstone mission, currently scheduled for launch in late 2011. Its primary science drivers are the composition, formation and evolution of the Galaxy. Gaia will not achieve its scientific requirements without detailed calibration and correction for radiation damage. Microscopic models of Gaia's CCDs are being developed to simulate the effect of radiation damage, charge trapping, which causes charge transfer inefficiency. The key to calculating the probability of a photoelectron being captured by a trap is the 3D electron density within each CCD pixel. However, this has not been physically modelled for Gaia CCD pixels. In this paper, the first of a series, we motivate the need for such specialised 3D device modelling and outline how its future results will fit into Gaia's overall radiation calibration strategy.

Long-term outcome of 56 dogs with nasal tumours treated with four doses of radiation at intervals of seven days.

PubMed

Mellanby, R J; Stevenson, R K; Herrtage, M E; White, R A S; Dobson, J M

2002-08-31

A retrospective study was undertaken on 56 dogs treated for nasal tumours by megavoltage radiotherapy with a hypofractionated schedule consisting of four doses of 9 Gy given at intervals of seven days. The dogs were followed until they died or were euthanased. The clinical signs had improved in 53 of the 56 dogs by the end of the treatment schedule. Mild acute radiation side effects were observed in the majority of the dogs but late radiation side effects were rare. Kaplan-Meier survival analysis revealed a median survival time after the final dose of radiation of 212 days. The one- and two-year survival rates were 45 per cent and 15 per cent. Fifty of the dogs were euthanased because the initial clinical signs recurred.

Transcriptome analysis reveals a stress response of Shewanella oneidensis deprived of background levels of ionizing radiation

PubMed Central

Li, Xiaoping; Schilkey, Faye; Smith, Geoffrey B.

2018-01-01

Natural ionizing background radiation has exerted a constant pressure on organisms since the first forms of life appeared on Earth, so that cells have developed molecular mechanisms to avoid or repair damages caused directly by radiation or indirectly by radiation-induced reactive oxygen species (ROS). In the present study, we investigated the transcriptional effect of depriving Shewanella oneidensis cultures of background levels of radiation by growing the cells in a mine 655 m underground, thus reducing the dose rate from 72.1 to 0.9 nGy h-1 from control to treatment, respectively. RNASeq transcriptome analysis showed the differential expression of 4.6 and 7.6% of the S. oneidensis genome during early- and late-exponential phases of growth, respectively. The greatest change observed in the treatment was the downregulation of ribosomal proteins (21% of all annotated ribosomal protein genes during early- and 14% during late-exponential) and tRNA genes (14% of all annotated tRNA genes in early-exponential), indicating a marked decrease in protein translation. Other significant changes were the upregulation of membrane transporters, implying an increase in the traffic of substrates across the cell membrane, as well as the up and downregulation of genes related to respiration, which could be interpreted as a response to insufficient oxidants in the cells. In other reports, there is evidence in multiple species that some ROS not just lead to oxidative stress, but act as signaling molecules to control cellular metabolism at the transcriptional level. Consistent with these reports, several genes involved in the metabolism of carbon and biosynthesis of amino acids were also regulated, lending support to the idea of a wide metabolic response. Our results indicate that S. oneidensis is sensitive to the withdrawal of background levels of ionizing radiation and suggest that a transcriptional response is required to maintain homeostasis and retain normal growth. PMID:29768440

Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration

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

Pixberg, Caroline; Koch, Raphael; Eich, Hans Theodor, E-mail: Hans.Eich@ukmuenster.de

Purpose: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae. Materials and Methods: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Asmore » of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity. Conclusions: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.« less

Salvage image guided radiation therapy to the prostate after cryotherapy failure.

PubMed

Hopper, Austin B; Sandhu, Ajay P S; Parsons, J Kellogg; Rose, Brent; Einck, John P

2018-01-01

Cryotherapy is an option for the primary treatment of localized prostate cancer, along with radical prostatectomy, external beam radiation therapy, and brachytherapy. Although it is known that local recurrence can occur in >20% of patients treated with primary cryotherapy, unfortunately there is a paucity of data on later salvage treatments. The use of external beam radiation therapy is an attractive option after cryotherapy failure, but there is little data on its efficacy and toxicity. We evaluated the biochemical control and complication rates of salvage dose-escalated image guided intensity modulated radiation therapy (IG-IMRT) after cryotherapy failure. Patients who were treated at our institution from 2005 to 2016 were reviewed for those who underwent cryotherapy as initial treatment followed by salvage IGRT. Patients were treated with dose-escalated IG-IMRT using standard treatment margins of 3 mm posterior and 7 mm in all other directions and daily cone beam computed tomography or kv imaging to implanted fiducial markers. Biochemical progression was defined in accordance with the Phoenix consensus conference definition. Eight patients were identified as having received post-cryotherapy salvage radiation within the study period. The median total dose was 77.7 Gy (range, 75.6-81.0 Gy). Median follow-up was 55 months (range, 6-88 months). Six patients remained biochemically controlled at the latest follow-up. One patient developed distant metastases after 22 months and one experienced biochemical failure at 30 months with no evidence of distant metastases. No patients experienced acute gastrointestinal toxicities of grade 2 or higher. There were no cases of late gastrointestinal or genitourinary toxicity. High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

NEW ULTRA-WIDE-FIELD ANGIOGRAPHIC GRADING SCHEME FOR RADIATION RETINOPATHY AFTER IODINE-125 BRACHYTHERAPY FOR UVEAL MELANOMA.

PubMed

McCannel, Tara A; Kim, EunAh; Kamrava, Mitchell; Lamb, James; Caprioli, Joseph; Yang, Dong; McCannel, Colin A

2017-10-06

Radiation retinopathy remains incompletely characterized and may cause severe vision loss. Ultra-wide-field fluorescein angiography provides a pan-fundus view of vascular alterations caused by radiation treatment and may predict visual and ocular outcomes. We have developed a grading scheme to describe pan-fundus severity and to predict the progression of radiation retinopathy in patients treated for uveal melanoma with iodine-125 brachytherapy. A retrospective review of patients treated with standard iodine-125 brachytherapy for uveal melanoma at the Ophthalmic Oncology Center at the University of California, Los Angeles, who had undergone both baseline and postbrachytherapy ultra-wide-field fluorescein angiography. A grading scheme was devised based on observations of vascular leakage, retinal perfusion status, and retinal proliferation. The correlation of grade severity with patient characteristics, tumor features, visual acuity, optical coherence tomography findings, and neovascular glaucoma was measured with chi-square and one-way analysis of variance analyses. Sixty-seven patients were identified for review. Consistent wide-field angiographic patterns after brachytherapy were observed and graded as follows: Grade 0: normal; Grade 1: late foveal leakage; Grade 2: late peripheral leakage; Grade 3: presence of nonperfusion; and Grade 4: retinal neovascularization. Six eyes (8.9%) were Grade 0; 16 (23.8%) were Grade 1; 25 (37.3%) were Grade 2; 16 (23.4%) were Grade 3; and 4 (6.0%) were Grade 4. Higher grade radiation severity correlated significantly with duration of follow-up (P < 0.02); younger age (P = 0.035); worse visual acuity (P = 0.001); cystoid macular edema or atrophy on optical coherence tomography (P < 0.0001); and neovascular glaucoma (P = 0.003). Wide-field fluorescein angiography revealed distinct fundus-wide patterns of vascular damage, which were progressive in nature in eyes treated with iodine-125 brachytherapy for uveal melanoma and correlated with signs of progressive vascular injury. This grading scheme may have prognostic value to predict the progression of radiation retinopathy and to prognosticate visual outcomes in patients undergoing brachytherapy.

Re-evaluation of the Haarlem Archaeopteryx and the radiation of maniraptoran theropod dinosaurs.

PubMed

Foth, Christian; Rauhut, Oliver W M

2017-12-02

Archaeopteryx is an iconic fossil that has long been pivotal for our understanding of the origin of birds. Remains of this important taxon have only been found in the Late Jurassic lithographic limestones of Bavaria, Germany. Twelve skeletal specimens are reported so far. Archaeopteryx was long the only pre-Cretaceous paravian theropod known, but recent discoveries from the Tiaojishan Formation, China, yielded a remarkable diversity of this clade, including the possibly oldest and most basal known clade of avialan, here named Anchiornithidae. However, Archaeopteryx remains the only Jurassic paravian theropod based on diagnostic material reported outside China. Re-examination of the incomplete Haarlem Archaeopteryx specimen did not find any diagnostic features of this genus. In contrast, the specimen markedly differs in proportions from other Archaeopteryx specimens and shares two distinct characters with anchiornithids. Phylogenetic analysis confirms it as the first anchiornithid recorded outside the Tiaojushan Formation of China, for which the new generic name Ostromia is proposed here. In combination with a biogeographic analysis of coelurosaurian theropods and palaeogeographic and stratigraphic data, our results indicate an explosive radiation of maniraptoran coelurosaurs probably in isolation in eastern Asia in the late Middle Jurassic and a rapid, at least Laurasian dispersal of the different subclades in the Late Jurassic. Small body size and, possibly, a multiple origin of flight capabilities enhanced dispersal capabilities of paravian theropods and might thus have been crucial for their evolutionary success.

NASA reload program

NASA Technical Reports Server (NTRS)

Byington, Marshall

1993-01-01

Atlantic Research Corporation (ARC) contracted with NASA to manufacture and deliver thirteen small scale Solid Rocket Motors (SRM). These motors, containing five distinct propellant formulations, will be used for plume induced radiation studies. The information contained herein summarizes and documents the program accomplishments and results. Several modifications were made to the scope of work during the course of the program. The effort was on hold from late 1991 through August, 1992 while propellant formulation changes were developed. Modifications to the baseline program were completed in late-August and Modification No. 6 was received by ARC on September 14, 1992. The modifications include changes to the propellant formulation and the nozzle design. The required motor deliveries were completed in late-December, 1992. However, ARC agreed to perform an additional mix and cast effort at no cost to NASA and another motor was delivered in March, 1993.

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

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

Murthy, Vedang, E-mail: vmurthy@actrec.gov.in; Masodkar, Renuka; Kalyani, Nikhil

Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gymore » in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.« less

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

PubMed Central

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM+/−) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM+/− cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage. PMID:12119422

Toxicity after post-prostatectomy image-guided intensity-modulated radiotherapy using Australian guidelines.

PubMed

Chin, Stephen; Aherne, Noel J; Last, Andrew; Assareh, Hassan; Shakespeare, Thomas P

2017-12-01

We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64-66 Gy IG-IMRT to the prostate bed between 2007 and 2015. Median follow-up after PPRT was 39 months. Baseline grade ≥2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade ≥2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade ≥4 toxicities. Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade ≥2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT. © 2017 The Royal Australian and New Zealand College of Radiologists.

Radiation effects in space

NASA Astrophysics Data System (ADS)

Fry, R. J. M.

The radiation protection guidelines of the National Aeronautics and Space Administration (NASA) are under review by Scientific Committe 75 of the National Council on Radiation Protection and Measurements. The re-evaluation of the current guidelines is necessary, first, because of the increase in information about radiation risks since 1970 when the original recommendations were made and second, the population at risk has changed. For example, women have joined the ranks of the astronauts. Two types of radiation, protons and heavy ions, are of particular concern in space. Unfortunately, there is less information about the effects on tissues and the induction of cancer by these radiations than by other radiations. The choice of Quality Factors (Q) for obtaining dose equivalents for these radiations, is an important aspect of the risk estimate for space travel. There are not sufficient data for the induction of late effects by either protons or by heavy ions. The current information suggests a RBE for the relative protons of about 1, whereas, -a RBE of 20 for tumor induction by heavy ions, such as iron-56, appears appropriate. The recommendations for the dose equivalent career limits for skin and the lens of the eye have been reduced but the 30-day and annual limits have been raised.

[Nonionizing radiation and electromagnetic fields].

PubMed

Bernhardt, J H

1991-01-01

Nonionising radiation comprises all kinds of radiation and fields of the electromagnetic spectrum where biological matter is not ionised, as well as mechanical waves such as infrasound and ultrasound. The electromagnetic spectrum is subdivided into individual sections and includes: Static and low-frequency electric and magnetic fields including technical applications of energy with mains frequency, radio frequency fields, microwaves and optic radiation (infrared, visible light, ultraviolet radiation including laser). The following categories of persons can be affected by emissions by non-ionising radiation: Persons in the environment and in the household, workers, patients undergoing medical diagnosis or treatment. If the radiation is sufficiently intense, or if the fields are of appropriate strength, a multitude of effects can occur (depending on the type of radiation), such as heat and stimulating or irritating action, inflammations of the skin or eyes, changes in the blood picture, burns or in some cases cancer as a late sequel. The ability of radiation to penetrate into the human body, as well as the types of interaction with biological tissue, with organs and organisms, differs significantly for the various kinds of nonionising radiation. The following aspects of nonionising radiation are discussed: protection of humans against excessive sunlight rays when sunbathing and when exposed to UV radiation (e.g. in solaria); health risks of radio and microwaves (safety of microwave cookers and mobile radio units); effects on human health by electric and magnetic fields in everyday life.

Impact of prognostic factors for postmastectomy radiation therapy of breast cancer patients

NASA Astrophysics Data System (ADS)

Simonov, K. A.; Startseva, Zh. A.; Slonimskaya, E. M.; Velikaya, V. V.

2017-09-01

The study included 196 breast cancer patients with stages T1-3N0-3M0. The comprehensive therapy for breast cancer included surgical operation, chemotherapy, and radiotherapy. Multivariate analysis showed that multifocality growth of tumor (p = 0.004), high grade III (p = 0.008), two metastatic lymph nodes (p = 0.02) were associated with an increased risk of regional node failure in the patients with one to three positive lymph nodes. The prognostic models describing the probability of local recurrences of breast cancer were developed for individualization of the radiation therapy tactics. Postmastectomy radiation therapy in the patients with high-risk breast cancer treated with modified radical mastectomy improves locoregional control, breast cancer-specific survival, does not increase late toxicity.

Gravitational collapse and Hawking-like radiation of a shell in AdS spacetime

NASA Astrophysics Data System (ADS)

Saini, Anshul; Stojkovic, Dejan

2018-01-01

In this paper, we study the collapse of a massive shell in 2 +1 and 3 +1 dimensional gravity with anti-de Sitter asymptotics. Using the Gauss-Codazzi method, we derive gravitational equations of motion of the shell. We then use the functional Schrödinger formalism to calculate the spectrum of particles produced during the collapse. At the late time, radiation agrees very well with the standard Hawking results. In 3 +1 dimensions, we reproduce the Hawking-Page transition. We then construct the density matrix of this collapsing system and analyze the information content in the emitted radiation. We find that the off-diagonal elements of the density matrix are very important in preserving the unitarity of the system.

Communication of benefits and risks of medical radiation: a historical perspective.

PubMed

Timins, Julie K

2011-11-01

X-rays were discovered by Wilhelm Röntgen in 1895. Within one year, benefits of x-rays, such as visualization of fractures, and detriments, such as x-ray dermatitis, were recognized. Nobel Laureates Pierre and Marie Sklodowska Curie discovered the radioactive element radium in 1898, and a year later the application of radiation to cure cancer was reported. A significant price was paid for this: Marie Curie died of aplastic anemia related to her radiation exposure, and her daughter Irene Joliot Curie, Nobelist for radiochemical research, died of radiation-induced leukemia. Internationally developed radiation protection recommendations were formalized starting in the late 1920s. The increasing use of ionizing radiation in medical diagnosis and radiation therapy has brought significant societal benefits. Known risks of therapeutic radiation include coronary artery disease and secondary malignancy. However, recently concerns have been raised of possible very small but incremental increases in malignancies due to diagnostic medical radiation. Patients are largely unaware of, and referring physicians and even radiologists often underestimate, the carcinogenic effects of radiation. There is a need to determine the appropriateness of imaging tests that use ionizing radiation prior to performance; optimize imaging protocols to reduce unnecessary radiation; include patients in the decision process and encourage and enable them to track their radiation exposure; and promote education about medical radiation to patients, referring physicians, radiologists, and members of the public. The basic radiation protection principles of justification, optimization, and application of dose limits still pertain.

Aircraft crew radiation workplaces: comparison of measured and calculated ambient dose equivalent rate data using the EURADOS in-flight radiation data base.

PubMed

Beck, Peter; Bartlett, David; Lindborg, Lennart; McAulay, Ian; Schnuer, Klaus; Schraube, Hans; Spurny, Frantisek

2006-01-01

In May 2000, the chairman of the European Radiation Dosimetry Group (EURADOS) invited a number of experts with experience of cosmic radiation dosimetry to form a working group (WG 5) on aircraft crew dosimetry. Three observers from the Article 31 Group of Experts as well as one observer from the Joint Aviation Authorities (JAA) were also appointed. The European Commission funded the meetings. Full meetings were organised in January 2001 and in November 2001. An editorial group, who are the authors of this publication, started late in 2002 to finalise a draft report, which was submitted to the Article 31 Group of Experts in June 2003. The methods and data reported are the product of the work of 26 research institutes from the EU, USA and Canada. Some of the work was supported by contracts with the European Commission, Directorate General XII, Science, Research and Development. A first overview of the EC report was published late in 2004. In this publication we focus on a comparison of measured and calculated ambient dose rate data using the EURADOS In-Flight Data Base. The evaluation of results obtained by different methods and groups, and comparison of measurement results and the results of calculations were performed in terms of the operational quantity ambient dose equivalent, H*(10). Aspects of measurement uncertainty are reported also. The paper discusses the estimation of annual doses for given flight hours and gives an outline of further research needed in the field of aircraft crew dosimetry, such as the influence of solar particle events.

The optimisation approach of ALARA in nuclear practice: an early application of the precautionary principle. Scientific uncertainty versus legal uncertainty.

PubMed

Lierman, S; Veuchelen, L

2005-01-01

The late health effects of exposure to low doses of ionising radiation are subject to scientific controversy: one view finds threats of high cancer incidence exaggerated, while the other view thinks the effects are underestimated. Both views have good scientific arguments in favour of them. Since the nuclear field, both industry and medicine have had to deal with this controversy for many decades. One can argue that the optimisation approach to keep the effective doses as low as reasonably achievable, taking economic and social factors into account (ALARA), is a precautionary approach. However, because of these stochastic effects, no scientific proof can be provided. This paper explores how ALARA and the Precautionary Principle are influential in the legal field and in particular in tort law, because liability should be a strong incentive for safer behaviour. This so-called "deterrence effect" of liability seems to evaporate in today's technical and highly complex society, in particular when dealing with the late health effects of low doses of ionising radiation. Two main issues will be dealt with in the paper: 1. How are the health risks attributable to "low doses" of radiation regulated in nuclear law and what lessons can be learned from the field of radiation protection? 2. What does ALARA have to inform the discussion of the Precautionary Principle and vice-versa, in particular, as far as legal sanctions and liability are concerned? It will be shown that the Precautionary Principle has not yet been sufficiently implemented into nuclear law.

Combination of external-beam radiotherapy with intraoperative electron-beam therapy is effective in incompletely resected pediatric malignancies.

PubMed

Oertel, Susanne; Niethammer, Andreas G; Krempien, Robert; Roeder, Falk; Eble, Michael J; Baer, Claudia; Huber, Peter E; Kulozik, Andreas; Waag, Karl-Ludwig; Treiber, Martina; Debus, Juergen

2006-01-01

Intraoperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In 1 child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients.

Glucose starvation impairs DNA repair in tumour cells selectively by blocking histone acetylation.

PubMed

Ampferl, Rena; Rodemann, Hans Peter; Mayer, Claus; Höfling, Tobias Tim Alexander; Dittmann, Klaus

2018-03-01

Tumour cells are characterized by aerobic glycolysis and thus have high glucose consumption. Because repairing radiation-induced DNA damage is an energy-demanding process, we hypothesized that glucose starvation combined with radiotherapy could be an effective strategy to selectively target tumour cells. We glucose-starved tumour cells (A549, FaDu) in vitro and analysed their radiation-induced cell responses compared to normal fibroblasts (HSF7). Irradiation depleted intracellular ATP levels preferentially in cancer cells. Consequently, glucose starvation impaired DNA double-strand break (DSB) repair and radiosensitized confluent tumour cells but not normal fibroblasts. In proliferating tumour cells glucose starvation resulted in a reduction of proliferation, but failed to radiosensitize cells. Glucose supply was indispensable during the late DSB repair in confluent tumour cells starting approximately 13 h after irradiation, and glucose starvation inhibited radiation-induced histone acetylation, which is essential for chromatin relaxation. Sirtinol - an inhibitor of histone deacetylases - reverted the effects of glucose depletion on histone acetylation and DNA DSB repair in tumour cells. Furthermore, a glucose concentration of 2.8 mmol/L was sufficient to impair DSB repair in tumour cells and reduced their clonogenic survival under a fractionated irradiation regimen. In resting tumour cells, glucose starvation combined with irradiation resulted in the impairment of late DSB repair and the reduction of clonogenic survival, which was associated with disrupted radiation-induced histone acetylation. However, in normal cells, DNA repair and radiosensitivity were not affected by glucose depletion. Copyright © 2017 Elsevier B.V. All rights reserved.

A Prospective Study of Proton Beam Reirradiation for Esophageal Cancer

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

Fernandes, Annemarie, E-mail: Annemarie.fernandes@gmail.com; Berman, Abigail T.; Mick, Rosemarie

Purpose: Reirradiation to the esophagus carries a significant risk of complications. Proton therapy may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of previously radiated normal tissues. Methods and Materials: Between June 2010 and February 2014, 14 patients with a history of thoracic radiation and newly diagnosed or locally recurrent esophageal cancer began proton beam reirradiation on a prospective trial. Primary endpoints were feasibility and acute toxicity. Toxicity was graded according Common Toxicity Criteria version 4.0. Results: The median follow-up was 10 months (2-25 months) from the start of reirradiation. Eleven patients receivedmore » concurrent chemotherapy. The median interval between radiation courses was 32 months (10-307 months). The median reirradiation prescription dose was 54.0 Gy (relative biological effectiveness [RBE]) (50.4-61.2 Gy[RBE]), and the median cumulative prescription dose was 109.8 Gy (76-129.4 Gy). Of the 10 patients who presented with symptomatic disease, 4 patients had complete resolution of symptoms, and 4 had diminished or stable symptoms. Two patients had progressive symptoms. The median time to symptom recurrence was 10 months. Maximum acute nonhematologic toxicity attributable to radiation was grade 2 (64%, N=9), 3 (29%, N=4), 4 (0%), and 5 (7%, N=1). The acute grade 5 toxicity was an esophagopleural fistula more likely related to tumor progression than radiation. Grade 3 nonhematologic acute toxicities included dysphagia, dehydration, and pneumonia. There was 1 late grade 5 esophageal ulcer more likely related to tumor progression than radiation. There were 4 late grade 3 toxicities: heart failure, esophageal stenosis requiring dilation, esophageal ulceration from tumor, and percutaneous endoscopic gastrostomy tube dependence. The median time to local failure was 10 months, and the median overall survival was 14 months. Conclusions: Our data demonstrate that proton reirradiation is feasible, with an encouraging symptom control rate, modest radiation-related toxicity, and favorable survival in this high-risk population.« less

Prophylaxis of radiation dermatitis with a topical cortisone cream

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

Potera, M.E.; Lookingbill, D.P.; Stryker, J.A.

Nineteen cancer patients receiving radiation therapy to the head, neck, chest wall, or abdomen were evaluated in a double-blind study to determine the effectiveness of 0.2% hydrocortisone valerate vs. placebo in reducing acute radiation dermatitis. Patients applied hydrocortisone valerate to one-half of the irradiated area and the placebo to the other half beginning two weeks after the initiation of radiotherapy and continuing until three weeks after completion. Left and right sides were scored each week with respect to erythema, dry desquamation, moist desquamation, ulceration, and the duration and intensity of symptoms such as soreness, burning, and itching. No statistically significantmore » difference was found between the 0.2% hydrocortisone valerate and the placebo in the acute skin response or the symptoms of radiation dermatitis. The patients were evaluated three months following radiotherapy for evidence of skin atrophy. There were no differences found between hydrocortisone valerate and the placebo with respect to the late effects of radiation therapy.« less

Prophylaxis of radiation dermatitis with a topical cortisone cream

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

Potera, M.E.; Lookingbill, D.P.; Stryker, J.A.

Nineteen cancer patients receiving radiation therapy to the head, neck, chest wall, or abdomen were evaluated in a double-blind study to determine the effectiveness of 0.2% hydrocortisone valerate vs placebo in reducing acute radiation dermatitis. Patients applied hydrocortisone valerate to one-half of the irradiated area and the placebo to the other half beginning two weeks after the initiation of radiotherapy and continuing until three weeks after completion. Left and right sides were scored each week with respect to erythema, dry desquamation, moist desquamation, ulceraton, and the duration and intensity of symptoms such as soreness, burning, and itching. No statistically significantmore » difference was found between the 0.2% hydrocortisone valerate and the placebo in the acute skin response or the symptoms of radiation dermatitis. The patients were evaluated three months following radiotherapy for evidence of skin atrophy. There was no difference found between hydrocortisone valerate and the placebo with respect to the late effects of radiation therapy.« less

Sulforaphane mitigates genotoxicity induced by radiation and anticancer drugs in human lymphocytes.

PubMed

Katoch, Omika; Kumar, Arun; Adhikari, Jawahar S; Dwarakanath, Bilikere S; Agrawala, Paban K

2013-12-12

Sulforaphane, present in cruciferous vegetables such as broccoli, is a dietary anticancer agent. Sulforaphane, added 2 or 20 h following phytohemaglutinin stimulation to cultured peripheral blood lymphocytes of individuals accidentally exposed to mixed γ and β-radiation, reduced the micronucleus frequency by up to 70%. Studies with whole blood cultures obtained from healthy volunteers confirmed the ability of sulforaphane to ameliorate γ-radiation-induced genotoxicity and to reduce micronucleus induction by other DNA-damaging anticancer agents, such as bleomycin and doxorubicin. This reduction in genotoxicity in lymphocytes treated at the G(0) or G(1) stage suggests a role for sulforaphane in modulating DNA repair. Sulforaphane also countered the radiation-induced increase in lymphocyte HDAC activity, to control levels, when cells were treated 2 h after exposure, and enhanced histone H4 acetylation status. Sulforaphane post-irradiation treatment enhanced the CD 34(+)Lin(-) cell population in culture. Sulforaphane has therapeutic potential for management of the late effects of radiation. Copyright © 2013 Elsevier B.V. All rights reserved.

Ultraviolet radiation from F and K stars and implications for planetary habitability.

PubMed

Kasting, J F; Whittet, D C; Sheldon, W R

1997-08-01

Now that extrasolar planets have been found, it is timely to ask whether some of them might be suitable for life. Climatic constraints on planetary habitability indicate that a reasonably wide habitable zone exists around main sequence stars with spectral types in the early-F to mid-K range. However, it has not been demonstrated that planets orbiting such stars would be habitable when biologically-damaging energetic radiation is also considered. The large amounts of UV radiation emitted by early-type stars have been suggested to pose a problem for evolving life in their vicinity. But one might also argue that the real problem lies with late-type stars, which emit proportionally less radiation at the short wavelengths (lambda < 200 nm) required to split O2 and initiate ozone formation. We show here that neither of these concerns is necessarily fatal to the evolution of advanced life: Earth-like planets orbiting F and K stars may well receive less harmful UV radiation at their surfaces than does the Earth itself.

Ultraviolet radiation from F and K stars and implications for planetary habitability

NASA Technical Reports Server (NTRS)

Kasting, J. F.; Whittet, D. C.; Sheldon, W. R.

1997-01-01

Now that extrasolar planets have been found, it is timely to ask whether some of them might be suitable for life. Climatic constraints on planetary habitability indicate that a reasonably wide habitable zone exists around main sequence stars with spectral types in the early-F to mid-K range. However, it has not been demonstrated that planets orbiting such stars would be habitable when biologically-damaging energetic radiation is also considered. The large amounts of UV radiation emitted by early-type stars have been suggested to pose a problem for evolving life in their vicinity. But one might also argue that the real problem lies with late-type stars, which emit proportionally less radiation at the short wavelengths (lambda < 200 nm) required to split O2 and initiate ozone formation. We show here that neither of these concerns is necessarily fatal to the evolution of advanced life: Earth-like planets orbiting F and K stars may well receive less harmful UV radiation at their surfaces than does the Earth itself.

Radiation-Related Treatment Effects across the Age Spectrum: Differences and Similarities or What The Old and Young Can Learn From Each Other

PubMed Central

Krasin, Matthew J.; Constine, Louis S.; Friedman, Debra; Marks, Lawrence B.

2010-01-01

Radiation related effects in children and adults limit the delivery of effective radiation doses and result in long-term morbidity affecting function and quality of life. Improvements in our understanding of the etiology and biology of these effects, including the influence of clinical variables, dosimetric factors, and the underlying biologic processes has made treatment safer and more efficacious. However, the approach to studying and understanding these effects differs between children and adults. By using the pulmonary and skeletal organ systems as examples, comparisons are made across the age spectrum for radiation related effects including pneumonitis, pulmonary fibrosis, osteonecrosis and fracture. Methods for dosimetric analysis, incorporation of imaging and biology as well a length of follow-up are compared, contrasted and discussed for both organ systems in children and adults. Better understanding of each age specific approach and how it differs may improve our ability to study late effects of radiation across the ages PMID:19959028

Radiative Amplification of Acoustic Waves in Hot Stars

NASA Technical Reports Server (NTRS)

Wolf, B. E.

1985-01-01

The discovery of broad P Cygni profiles in early type stars and the detection of X-rays emitted from the envelopes of these stars made it clear, that a considerable amount of mechanical energy has to be present in massive stars. An attack on the problem, which has proven successful when applied to late type stars is proposed. It is possible that acoustic waves form out of random fluctuations, amplify by absorbing momentum from stellar radiation field, steepen into shock waves and dissipate. A stellar atmosphere was constructed, and sinusoidal small amplitude perturbations of specified Mach number and period at the inner boundary was introduced. The partial differential equations of hydrodynamics and the equations of radiation transfer for grey matter were solved numerically. The equation of motion was augmented by a term which describes the absorption of momentum from the radiation field in the continuum and in lines, including the Doppler effect and allows for the treatment of a large number of lines in the radiative acceleration term.

Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review

PubMed Central

Laube, Markus; Kniess, Torsten; Pietzsch, Jens

2016-01-01

Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents. PMID:27104573

Sterilizing effects of cobalt-60 and cesium-137 radiation on male sea lampreys

USGS Publications Warehouse

Hanson, L.H.

1990-01-01

Male spawning-run sea lampreys Petromyzon marinus were exposed to various doses of cobalt-60 or cesium-137 radiation in an attempt to sterilize them for use in a program for controlling sea lampreys through the release of sterile males. Males captured and irradiated during the early part of the upstream migration were not effectively sterilized at the doses tested. After irradiation, the sea lampreys were more susceptible to fungal infections by Saprolegnia sp., and many died without attempting to spawn. Males captured and irradiated during the middle and late parts of the spawning migration were effectively sterilized at a dose of 2,000 rads. However, some radiation-induced mortality was observed in males captured and irradiated during the middle part of the spawning migration. Radiation is not as effective as the chemosterilant bisazir for sterilizing male sea lampreys.

Laboratory analogue of a supersonic accretion column in a binary star system.

PubMed

Cross, J E; Gregori, G; Foster, J M; Graham, P; Bonnet-Bidaud, J-M; Busschaert, C; Charpentier, N; Danson, C N; Doyle, H W; Drake, R P; Fyrth, J; Gumbrell, E T; Koenig, M; Krauland, C; Kuranz, C C; Loupias, B; Michaut, C; Mouchet, M; Patankar, S; Skidmore, J; Spindloe, C; Tubman, E R; Woolsey, N; Yurchak, R; Falize, É

2016-06-13

Astrophysical flows exhibit rich behaviour resulting from the interplay of different forms of energy-gravitational, thermal, magnetic and radiative. For magnetic cataclysmic variable stars, material from a late, main sequence star is pulled onto a highly magnetized (B>10 MG) white dwarf. The magnetic field is sufficiently large to direct the flow as an accretion column onto the poles of the white dwarf, a star subclass known as AM Herculis. A stationary radiative shock is expected to form 100-1,000 km above the surface of the white dwarf, far too small to be resolved with current telescopes. Here we report the results of a laboratory experiment showing the evolution of a reverse shock when both ionization and radiative losses are important. We find that the stand-off position of the shock agrees with radiation hydrodynamic simulations and is consistent, when scaled to AM Herculis star systems, with theoretical predictions.

The Radiation Belt Storm Probes (RBSP) Energetic Particle, Composition, and Thermal plasma (ECT) Suite: Upcoming Opportunties for Testing Radiation Belt Acceleration Mechanisms

NASA Astrophysics Data System (ADS)

Spence, Harlan; Reeves, Geoffrey

2012-07-01

The Radiation Belt Storm Probes (RBSP) mission will launch in late summer 2012 and begin its exploration of acceleration and dynamics of energetic particles in the inner magnetosphere. In this presentation, we discuss opportunities afforded by the RBSP Energetic Particle, Composition, and Thermal plasma (ECT) instrument suite to advance our understanding of acceleration processes in the radiation belts. The RBSP-ECT instrument suite comprehensively measures the electron and major ion populations of the inner magnetosphere, from the lowest thermal plasmas of the plasmasphere, to the hot plasma of the ring current, to the relativistic populations of the radiation belts. Collectively, the ECT measurements will reveal the complex cross-energy coupling of these colocated particle populations, which along with concurrent RBSP wave measurements, will permit various wave-particle acceleration mechanisms to be tested. We review the measurement capabilities of the RBSP-ECT instrument suite, and demonstrate several examples of how these measurements will be used to explore candidate acceleration mechanisms and dynamics of radiation belt particles.

Sequelae of abdominal radiation and their medical management

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

McLaren, J.R.

1977-02-01

As various chemotherapeutic agents are added to treatment routines, the possibility of adverse effects is appreciably increased, particularly in those organs for which the agents have specific toxicity. Symptoms most commonly associated with radiation sickness, such as malaise, anorexia, nausea, vomiting, diarrhea, dysphagia, dermatitis, and depleted hemopoietic elements, are usually seen late in the course of radiation therapy or shortly thereafter. Consequently, they are managed by the physician in charge of radiation or the patient's referring physician. The general physician may be concerned with symptoms arising from delayed organ pathology. These symptoms may arise in many tissues that are stillmore » considered somewhat radioresistant, but secondary to sequelae arising because of connective tissue changes from obliterative narrowing of the finer vasculature. Radiation may be only one of several possible causes, and the symptoms of sequelae may appear only after a long latent period, so that the previous radiation may not be considered in the differential diagnosis unless a detailed history is taken. The medical management of these sequelae is, in general, similar to that used for the pathology produced in these organs by other agents.« less

Retrospective study of orthovoltage radiation therapy for nasal tumors in 42 dogs.

PubMed

Northrup, N C; Etue, S M; Ruslander, D M; Rassnick, K M; Hutto, D L; Bengtson, A; Rand, W; Moore, A S

2001-01-01

Megavoltage radiation therapy currently is the standard of care for dogs with nasal tumors. Some studies report that surgery and adjunctive orthovoltage radiation therapy result in longer control of these tumors than does megavoltage radiation therapy alone. This study reports less effective control of nasal tumors in dogs treated with surgery and orthovoltage radiation than previously observed, supporting the superiority of megavoltage radiation therapy for these tumors. In addition, this study suggests 2 new prognostic indicators for dogs with nasal tumors and describes toxicity associated with surgery and orthovoltage therapy. Forty-two dogs with nasal tumors were treated with surgical cytoreduction and 48 Gy orthovoltage radiation therapy administered in twelve 4-Gy fractions. Median survival was 7.4 months. One- and 2-year survival rates were 37% and 17%, respectively. Dogs with facial deformity had shorter survival than those without deformity (P = .005). Dogs with resolution of clinical signs after treatment had longer survival than those with chronic nasal signs (P = .0001). Acute radiation toxicity was moderate to severe for skin and eye and negligible for oral mucosa. Toxicity healed within 1 month after radiation therapy. Late toxicity was mild, but 70% of evaluable dogs experienced persistent ocular signs. Only 39% of dogs achieved a disease-free period.

Properties of an ultrarelativistic charged particle radiation in a constant homogeneous crossed electromagnetic field

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

Bogdanov, O.V., E-mail: bov@tpu.ru; Department of Higher Mathematics and Mathematical Physics, Tomsk Polytechnic University, Tomsk, 634050; Kazinski, P.O., E-mail: kpo@phys.tsu.ru

The properties of radiation created by a classical ultrarelativistic scalar charged particle in a constant homogeneous crossed electromagnetic field are described both analytically and numerically with radiation reaction taken into account in the form of the Landau–Lifshitz equation. The total radiation naturally falls into two parts: the radiation formed at the entrance point of a particle into the crossed field (the synchrotron entrance radiation), and the radiation coming from the late-time asymptotics of a particle motion (the de-excited radiation). The synchrotron entrance radiation resembles, although does not coincide with, the ultrarelativistic limit of the synchrotron radiation: its distribution over energiesmore » and angles possesses almost the same properties. The de-excited radiation is soft, not concentrated in the plane of motion of a charged particle, and almost completely circularly polarized. The photon energy delivering the maximum to its spectral angular distribution decreases with increasing the initial energy of a charged particle, while the maximum value of this distribution remains the same at the fixed photon observation angle and entrance angle of a charged particle. The ultraviolet and infrared asymptotics of the total radiation are also described. - Highlights: • Properties of an electron radiation in a crossed electromagnetic field are studied. • Spectral angular distribution of the synchrotron entrance radiation is described. • Spectral angular distribution of the de-excited radiation is described. • De-excited radiation is almost completely circularly polarized. • Photon energy at the maximum of the de-excited radiation decreases with increasing the initial energy of an electron.« less

Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

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

Kato, Shingo, E-mail: s_kato@saitama-med.ac.jp; National Institute of Radiological Sciences of Japan, Chiba; Ohno, Tatsuya

2013-09-01

Purpose: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Methods and Materials: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m{sup 2}) were administered during the course of radiation therapy. Treatment results were evaluatedmore » by the rates of local control, overall survival, and late toxicities. Results: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. Conclusions: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.« less

Safety of dose escalation by simultaneous integrated boosting radiation dose within the primary tumor guided by (18)FDG-PET/CT for esophageal cancer.

PubMed

Yu, Wen; Cai, Xu-Wei; Liu, Qi; Zhu, Zheng-Fei; Feng, Wen; Zhang, Qin; Zhang, Ying-Jian; Yao, Zhi-Feng; Fu, Xiao-Long

2015-02-01

To observe the safety of selective dose boost to the pre-treatment high (18)F-deoxyglucose (FDG) uptake areas of the esophageal GTV. Patients with esophageal squamous cell carcinoma were treated with escalating radiation dose of 4 levels, with a simultaneous integrated boost (SIB) to the pre-treatment 50% SUVmax area of the primary tumor. Patients received 4 monthly cycles of cisplatin and fluorouracil. Dose-limiting toxicity (DLT) was defined as any Grade 3 or higher acute toxicities causing continuous interruption of radiation for over 1 week. From April 2012 to February 2014, dose has been escalated up to LEVEL 4 (70Gy). All of the 25 patients finished the prescribed dose without DLT, and 10 of them developed Grade 3 acute esophagitis. One patient of LEVEL 2 died of esophageal hemorrhage within 1 month after completion of radiotherapy, which was not definitely correlated with treatment yet. Late toxicities remained under observation. With median follow up of 8.9months, one-year overall survival and local control was 69.2% and 77.4%, respectively. Dose escalation in esophageal cancer based on (18)FDG-PET/CT has been safely achieved up to 70Gy using the SIB technique. Acute toxicities were well tolerated, whereas late toxicities and long-term outcomes deserved further observation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Late G1 accumulation after 2 Gy of gamma-irradiation is related to endogenous Raf-1 protein expression and intrinsic radiosensitivity in human cells.

PubMed Central

Warenius, H. M.; Jones, M.; Jones, M. D.; Browning, P. G.; Seabra, L. A.; Thompson, C. C.

1998-01-01

We have previously reported a correlation between high endogenous expression of the protein product of the RAF-1 proto-oncogene, intrinsic cellular radiosensitivity and rapid exit from a G2/M delay induced by 2 Gy of gamma-irradiation. Raf1 is a positive serine/threonine kinase signal transduction factor that relays signals from the cell membrane to the MAP kinase system further downstream and is believed to be involved in an ionizing radiation signal transduction pathway modulating the G1/S checkpoint. We therefore extended our flow cytometric studies to investigate relationships between radiosensitivity, endogenous expression of the Raf1 protein and perturbation of cell cycle checkpoints, leading to alterations in the G1, S and G2/M populations after 2 Gy of gamma-irradiation. Differences in intrinsic radiosensitivity after modulation of the G1/S checkpoint have generally been understood to involve p53 function up to the present time. A role for dominant oncogenes in control of G1/S transit in radiation-treated cells has not been identified previously. Here, we show in 12 human in vitro cancer cell lines that late G1 accumulation after 2 Gy of radiation is related to both Raf1 expression (r = 0.91, P = 0.0001) and the radiosensitivity parameter SF2 (r = -0.71, P = 0.009). PMID:9579826

A simple model of universe describing the early inflation and the late accelerated expansion in a symmetric manner

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

Chavanis, Pierre-Henri

We construct a simple model of universe which 'unifies' vacuum energy and radiation on the one hand, and matter and dark energy on the other hand in the spirit of a generalized Chaplygin gas model. Specifically, the phases of early inflation and late accelerated expansion are described by a generalized equation of state p/c{sup 2} = αρ+kρ{sup 1+1/n} having a linear component p = αρc{sup 2} and a polytropic component p = kρ{sup 1+1/n}c{sup 2}. For α= 1/3, n= 1 and k=−4/(3ρ{sub P}), where ρ{sub P}= 5.1610{sup 99} g/m{sup 3} is the Planck density, this equation of state describes themore » transition between the vacuum energy era and the radiation era. For t≥ 0, the universe undergoes an inflationary expansion that brings it from the Planck size l{sub P}= 1.6210{sup −35} m to a size a{sub 1}= 2.6110{sup −6} m on a timescale of about 23.3 Planck times t{sub P}= 5.3910{sup −44} s (early inflation). When t > t{sub 1}= 23.3t{sub P}, the universe decelerates and enters in the radiation era. We interpret the transition from the vacuum energy era to the radiation era as a second order phase transition where the Planck constant ℏ plays the role of finite size effects (the standard Big Bang theory is recovered for ℏ= 0). For α= 0, n=−1 and k=−ρ{sub Λ}, where ρ{sub Λ}= 7.0210{sup −24} g/m{sup 3} is the cosmological density, the equation of state p/c{sup 2} = αρ+kρ{sup 1+1/n} describes the transition from a decelerating universe dominated by pressureless matter (baryonic and dark matter) to an accelerating universe dominated by dark energy (late inflation). This transition takes place at a size a{sub 2}= 0.204l{sub Λ}. corresponding to a time t{sub 2}= 0.203t{sub Λ} where l{sub Λ}= 4.38 10{sup 26} m is the cosmological length and t{sub Λ}= 1.46 10{sup 18} s the cosmological time. The present universe turns out to be just at the transition between these two periods (t{sub 0}∼t{sub 2}). Our model gives the same results as the standard ΛCDM model for t≫t{sub P} and completes it by incorporating a phase of early inflation for t < 23.3t{sub P} in a very natural manner. Furthermore, it reveals a nice 'symmetry' between the early and the late evolution of the universe. The early universe is modeled by a polytrope n=+ 1 and the late universe by a polytrope n=−1. Furthermore, the cosmological constant Λ in the late universe plays a role similar to the Planck constant ℏ in the early universe. The mathematical formulae in the early and in the late universe are then strikingly symmetric. We interpret the cosmological constant as a fundamental constant of Nature describing the 'cosmophysics' just like the Planck constant describes the 'microphysics'. The Planck density and the cosmological density represent fundamental upper and lower bounds differing by 122 orders of magnitude. The cosmological constant 'problem' may be a false problem. Finally, we show that our model admits a scalar field interpretation based on a quintessence field or a tachyon field.« less

The Riemann-Hilbert approach to the Helmholtz equation in a quarter-plane: Neumann, Robin and Dirichlet boundary conditions

NASA Astrophysics Data System (ADS)

Its, Alexander; Its, Elizabeth

2018-04-01

We revisit the Helmholtz equation in a quarter-plane in the framework of the Riemann-Hilbert approach to linear boundary value problems suggested in late 1990s by A. Fokas. We show the role of the Sommerfeld radiation condition in Fokas' scheme.

Nuclear Power: The Market Test. Worldwatch Paper 57.

ERIC Educational Resources Information Center

Flavin, Christopher

Nuclear power was considered vital to humanity's future until just a short time ago. Since the late seventies, economic viability has joined a list of such issues as waste disposal and radiation hazards which call into question the future of nuclear power. This document discusses (in separate sections): (1) the selling of nuclear power, including…

Taking Care of You and Your Baby While You're Pregnant

MedlinePlus

... pregnancy varies for each person. Your job and work environment play a big role. For instance, radiation, lead and other materials, such as copper and mercury, can be harmful to your baby. If your job is active, you may not be able to work as late. Desk jobs are not thought to ...

Surgical Treatment of Anorectal Crohn Disease

PubMed Central

Lewis, Robert T.; Bleier, Joshua I. S.

2013-01-01

Crohn disease involves the perineum and rectum in approximately one-third of patients. Symptoms can range from mild, including skin tags and hemorrhoids, to unremitting and severe, requiring a proctectomy in a small, but significant, portion. Fistula-in-ano and perineal sepsis are the most frequent manifestation seen on presentation. Careful diagnosis, including magnetic resonance imaging or endorectal ultrasound with examination under anesthesia and aggressive medical management, usually with a tumor necrosis factor-alpha, is critical to success. Several options for definitive surgical repair are discussed, including fistulotomy, fibrin glue, anal fistula plug, endorectal advancement flap, and ligation of intersphincteric fistula tract procedure. All suffer from decreased efficacy in patients with Crohn disease. In the presence of active proctitis or perineal disease, no surgical therapy other than drainage of abscesses and loose seton placement is recommended, as iatrogenic injury and poor wound healing are common in that scenario. PMID:24436656

Lymphogranuloma venereum genovar L2b concomitantly with syphilis and hepatitis C in a male patient in Poland – case report

PubMed

Serwin, Agnieszka Beata; Koper, Marta; Unemo, Magnus

2018-01-01

We describe the first case of lymphogranuloma venereum (LGV) in Poland, with inguino-femoral lymphadenopathy, diagnosed and successfully treated according to the 2013 European LGV guideline. Chlamydia trachomatis genovar L2b, mainly responsible for the ongoing LGV epidemics among men who have sex with men (MSM) in Western European countries, was confirmed. The case also verified that co-infections with other sexually transmitted infections (syphilis and hepatitis C virus) are frequent in MSM LGV patients, as well as the very large difficulties with contact tracing for these patients. LGV needs to be considered in the diagnosis of inguinal lymph nodes inflammation or proctitis, especially in MSM. It is also crucial to have access to appropriate laboratory diagnostic methods in order to screen for and confirm all LGV cases by typing C. trachomatis genovars.

Emergence of the lymphogranuloma venereum L2c genovariant, Hungary, 2012 to 2016.

PubMed

Petrovay, Fruzsina; Balla, Eszter; Erdősi, Tímea

2017-02-02

In eastern Europe, few countries have so far reported laboratory-confirmed cases of lymphogranuloma venereum (LGV). Here we describe 22 LGV cases in men who have sex with men (MSM) detected in Hungary from November 2012 to July 2016. Sequence analyses show that 16 of these 22 cases were affected by the L2c genovariant, with from 2012 to 2014, one LGV L2c case detected per year, followed by seven cases in 2015 and six up to July 2016. Of the 16 total L2c LGV cases, 10 had severe haemorrhagic proctitis. These findings are concerning as cases with this new genovariant among MSM have not been frequently reported in Europe to date. More research is needed to assess the spread of the L2c genovariant and its potential association with virulence and severe clinical manifestation. This article is copyright of The Authors, 2017.

Emergence of the lymphogranuloma venereum L2c genovariant, Hungary, 2012 to 2016

PubMed Central

Petrovay, Fruzsina; Balla, Eszter; Erdősi, Tímea

2017-01-01

In eastern Europe, few countries have so far reported laboratory-confirmed cases of lymphogranuloma venereum (LGV). Here we describe 22 LGV cases in men who have sex with men (MSM) detected in Hungary from November 2012 to July 2016. Sequence analyses show that 16 of these 22 cases were affected by the L2c genovariant, with from 2012 to 2014, one LGV L2c case detected per year, followed by seven cases in 2015 and six up to July 2016. Of the 16 total L2c LGV cases, 10 had severe haemorrhagic proctitis. These findings are concerning as cases with this new genovariant among MSM have not been frequently reported in Europe to date. More research is needed to assess the spread of the L2c genovariant and its potential association with virulence and severe clinical manifestation. PMID:28183394

Too hot to handle? Analytic solutions for massive neutrino or warm dark matter cosmologies

NASA Astrophysics Data System (ADS)

Slepian, Zachary; Portillo, Stephen K. N.

2018-05-01

We obtain novel closed-form solutions to the Friedmann equation for cosmological models containing a component whose equation of state is that of radiation (w = 1/3) at early times and that of cold pressureless matter (w = 0) at late times. The equation of state smoothly transitions from the early to late-time behavior and exactly describes the evolution of a species with a Dirac Delta function distribution in momentum magnitudes |p_0| (i.e. all particles have the same |p_0|). Such a component, here termed "hot matter", is an approximate model for both neutrinos and warm dark matter. We consider it alone and in combination with cold matter and with radiation, also obtaining closed-form solutions for the growth of super-horizon perturbations in each case. The idealized model recovers t(a) to better than 1.5% accuracy for all a relative to a Fermi-Dirac distribution (as describes neutrinos). We conclude by adding the second moment of the distribution to our exact solution and then generalizing to include all moments of an arbitrary momentum distribution in a closed-form solution.

Too hot to handle? Analytic solutions for massive neutrino or warm dark matter cosmologies

NASA Astrophysics Data System (ADS)

Slepian, Zachary; Portillo, Stephen K. N.

2018-07-01

We obtain novel closed-form solutions to the Friedmann equation for cosmological models containing a component whose equation of state is that of radiation (w = 1/3) at early times and that of cold pressureless matter (w= 0) at late times. The equation of state smoothly transitions from the early- to late-time behaviour and exactly describes the evolution of a species with a Dirac delta function distribution in momentum magnitudes |{p}_0| (i.e. all particles have the same |{p}_0|). Such a component, here termed `hot matter', is an approximate model for both neutrinos and warm dark matter. We consider it alone and in combination with cold matter and with radiation, also obtaining closed-form solutions for the growth of superhorizon perturbations in each case. The idealized model recovers t(a) to better than 1.5 per cent accuracy for all a relative to a Fermi-Dirac distribution (as describes neutrinos). We conclude by adding the second moment of the distribution to our exact solution and then generalizing to include all moments of an arbitrary momentum distribution in a closed-form solution.

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

NASA Astrophysics Data System (ADS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or γ rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for γ rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Space Radiation and Risks to Human Health

NASA Technical Reports Server (NTRS)

Huff, Janice L.

2014-01-01

The radiation environment in space poses significant challenges to human health and is a major concern for long duration manned space missions. Outside the Earth's protective magnetosphere, astronauts are exposed to higher levels of galactic cosmic rays, whose physical characteristics are distinct from terrestrial sources of radiation such as x-rays and gamma-rays. Galactic cosmic rays consist of high energy and high mass nuclei as well as high energy protons; they impart unique biological damage as they traverse through tissue with impacts on human health that are largely unknown. The major health issues of concern are the risks of radiation carcinogenesis, acute and late decrements to the central nervous system, degenerative tissue effects such as cardiovascular disease, as well as possible acute radiation syndromes due to an unshielded exposure to a large solar particle event. The NASA Human Research Program's Space Radiation Program Element is focused on characterization and mitigation of these space radiation health risks along with understanding these risks in context of the other biological stressors found in the space environment. In this overview, we will provide a description of these health risks and the Element's research strategies to understand and mitigate these risks.

Induction of genomic instability after an acute whole-body exposure of mice to 56Fe ions

NASA Astrophysics Data System (ADS)

Rithidech, Kanokporn; Supanpaiboon, Wisa; Whorton, Elbert

Different types of galactic cosmic rays (GCR) are present in space and have large mass and energy (HZE particles). Among these, stripped 56 Fe ions are of major concern. Although HZE particles are approximately 1% of GCR, their contribution to health risk could be significant because of (1) their high linear energy transfer (LET) resulting in a larger amount of energy being deposited in the hit cells, and (2) the lack of information on the effectiveness of these particles in cancer induction. To better protect astronauts in space environments, it is essential that we improve our understanding of the 56 Fe-ion-induced damage associated with the increased risk of late occurring diseases (such as cancer). It has been well established that acute myeloid leukemia (AML) is one of the major malignancies associated with exposure to ionizing radiation in both human beings and in mice. It is therefore one of the most important cancers related to space flights. For these reasons, it is important to investigate 56 Fe ion-induced damage in in vivo systems, especially in those cells that are known to be at risk for health problems associated with radiation, such as hematopoietic cells, the known target cell for radiation-induced leukemia. Since in vivo studies of humans are not possible, animal studies are critically important. It has been widely suggested that elevation of delayed chromosomal damage (normally known as genomic instability) is associated with cancer risk. We therefore determined dose-response relationships for the frequencies of micronuclei (MN) in mouse blood erythrocytes as a measure of both initial radiation damage and the induction of genomic instability. The frequencies of MN were measured in mature normochromatic-erythrocytes (MN-NCEs) and immature polychromatic-erythrocytes (MN-PCEs). These measurements were made as a function of radiation dose, radiation quality, time after irradiation and the genetic background of exposed mice. Blood samples were collected from CBA/CaJ and C57BL/6J mice at different times up to 3 months following an acute whole-body exposure to various doses of 1 GeV/amu 56 Fe ions (0, 0.1, 0.5 and 1.0 cGy) or 137 Cs gamma rays (0, 0.5, 1.0 and 3.0 cGy, as a reference radiation). These strains of mouse are known to be sensitive (CBA/CaJ) or resistant (C57BL/6J) to radiation-induced chromosomal damage and AML. At 2 days after the exposure, our data indicated that there was no increase in the frequency of MN-PCEs in CBA/CaJ mice exposed to 56 Fe ions while the frequency of MN-PCEs elevated as a function of dose in the C57BL/6J mice. At day 4, there was no dose related increase in either strain of mouse exposed to either 56 Fe ions or 137 Cs gamma rays. We also found that at the early sacrifice times (2 and 4 days) the 56 Fe ions were slightly more effective, per unit dose, in inducing MN-NCEs than 137 Cs gamma rays in both strains. Likewise, no increase in the frequency of MN-NCEs was found at late times after an acute exposure to either type of radiation. In contrast, both types of radiation induced increased MN-PCE frequencies in irradiated CBA/CaJ mice, but not C57BL/6J mice, at late times post-exposure. This finding indicates the potential induction of genomic instability in hematopoietic cells of CBA/CaJ mice by both types of radiation. The finding also demonstrates the influence of genetic background on radiation-induced genomic instability in vivo. Research funded by NASA Grant #NAG9- 1 52 .

SU-F-T-01: Optimization of the Accelerated Partial Breast Brachytherapy Fractionation with Consideration of Physical Doses to Tumor and Organ at Risk

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

Fu, W; Huq, M

2016-06-15

Purpose: The accelerated partial breast irradiation (APBI) with brachytherapy prescribes 34Gy to be delivered in 10 fractions over 5 consecutive working days without considering the physical dose to the target and organs at risk (OARs) for an individual patient. The purpose of this study is to optimize the fractionation scheme by evaluating the radiation effect on tumor and OARs with a modified linear-quadratic (LQ) model based on dose-volume histograms (DVHs). Methods: Five breast patients treated with multilumen balloon brachytherapy were selected. The minimum skin and rib spacing were ranged from 2.5mm to 14.3mm and from 1.0mm to 25.0mm, respectively. Themore » LQ model parameters were set as: (1) breast: α=0.08, β=0.028, doubling time Tpot=14.4 days, and starting time Tk=21days; (2) skin: acute reaction α=0.101, β=0.009; late reaction α=0.064, β=0.029; (3) rib: α=0.3, β=0.12. Boundary dose Dt was 6 Gy for both target and OARs. The relation between radiation effects on the tumor (ET) and OARs (EOAR) were plotted for fraction number from 1 to 20. Results: The value of radiation effect from routine 3.4Gyx10 fractions was used as reference, ETref and EOARref. If set ET=ETref, the fractionation that results in minimum EOAR values correspond to the optimal fractionation. For these patients, the optimal numbers are 10 fractions for skin acute reaction, 18 fractions for skin and rib late reaction while the doses per fraction are 3.4Gy and 2.05–2.10Gy, respectively. If set EOAR=EOARref, the fractionation that results in a maximum ET value corresponds to the optimal fractionation. The optimal fractionation is 3.4Gyx10 fractions for skin acute reaction, and 2.10–2.25Gyx18 fractions for skin late reaction and rib. Conclusion: For APBI brachytherapy, the routine 3.4Gyx10 fractions is optimal fractionation for skin acute reaction, while 2.05–2.25Gyx18 fractions is optimal fractionation for late reaction of skin and rib.« less

A systematic review of publications on charged particle therapy for hepatocellular carcinoma.

PubMed

Igaki, Hiroshi; Mizumoto, Masashi; Okumura, Toshiyuki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Sakurai, Hideyuki

2018-06-01

Charged particle therapy (proton beam therapy and carbon ion therapy) is a form of radiotherapy which has the unique characteristic of superior depth dose distribution, and has been used for the treatment of hepatocellular carcinoma (HCC) in a limited number of patients, especially in Japan. We undertook a systematic review to define the clinical utility of charged particle therapy for patients with HCC. We searched the MEDLINE database from 1983 to June 2016 to identify clinical studies on charged particle therapy for HCC. Primary outcomes of interest were local control, overall survival, and late radiation morbidities. A total of 13 cohorts from 11 papers were selected from an initial dataset of 78 papers. They included a randomized controlled trial comparing proton beam therapy with transarterial chemoembolization, 9 phase I or II trials and 2 retrospective studies. The reported actuarial local control rates ranged from 71.4-95% at 3 years, and the overall survival rates ranged from 25-42.3% at 5 years. Late severe radiation morbidities were uncommon, and a total of 18 patients with grade ≥3 late adverse events were reported among the 787 patients included in this analysis. Charged particle therapy for HCC was associated with good local control with limited probability of severe morbidities. The cost-effectiveness and the distinctive clinical advantages of charged particle therapies should be clarified in order to become a socially accepted treatment modality for HCC.

Spot-Scanning Proton Radiation Therapy for Pediatric Chordoma and Chondrosarcoma: Clinical Outcome of 26 Patients Treated at Paul Scherrer Institute

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

Rombi, Barbara; ATreP; Ares, Carmen, E-mail: carmen.ares@psi.ch

Purpose: To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. Methods and Materials: Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose ofmore » 1.8-2.0 Gy (RBE) per fraction. Results: Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. Conclusions: Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.« less

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

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

Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian

Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating verymore » good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.« less

Postradiation atrophy of mature bone

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

Ergun, H.; Howland, W.J.

1980-01-01

The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. The differentiationmore » of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.« less

Reinterpretation of Mariner 9 IRIS data on the basis of a simulation of radiative-conductive convective transfer in the dust laden Martian atmosphere

NASA Technical Reports Server (NTRS)

Pallman, A. J.

1974-01-01

Time dependent vertical distributions of atmospheric temperature and static stability were determined by a radiative-convective-conductive heat transfer model attuned to Mariner 9 IRIS radiance data. Of particular interest were conditions of both the dust-laden and dust-free atmosphere in the middle latitudes on Mars during the late S.H. summer season. The numerical model simulates at high spatial and temporal resolution (52 atmospheric and 30 subsurface levels; with a time-step of 7.5 min.) the heat transports in the ground-atmosphere system. The algorithm is based on the solution of the appropriate heating rate equation which includes radiative, molecular-conductive and convective heat transfer terms. Ground and atmosphere are coupled by an internal thermal boundary condition.

The Sail-Backed Reptile Ctenosauriscus from the Latest Early Triassic of Germany and the Timing and Biogeography of the Early Archosaur Radiation

PubMed Central

Butler, Richard J.; Brusatte, Stephen L.; Reich, Mike; Nesbitt, Sterling J.; Schoch, Rainer R.; Hornung, Jahn J.

2011-01-01

Background Archosaurs (birds, crocodilians and their extinct relatives including dinosaurs) dominated Mesozoic continental ecosystems from the Late Triassic onwards, and still form a major component of modern ecosystems (>10,000 species). The earliest diverse archosaur faunal assemblages are known from the Middle Triassic (c. 244 Ma), implying that the archosaur radiation began in the Early Triassic (252.3–247.2 Ma). Understanding of this radiation is currently limited by the poor early fossil record of the group in terms of skeletal remains. Methodology/Principal Findings We redescribe the anatomy and stratigraphic position of the type specimen of Ctenosauriscus koeneni (Huene), a sail-backed reptile from the Early Triassic (late Olenekian) Solling Formation of northern Germany that potentially represents the oldest known archosaur. We critically discuss previous biomechanical work on the ‘sail’ of Ctenosauriscus, which is formed by a series of elongated neural spines. In addition, we describe Ctenosauriscus-like postcranial material from the earliest Middle Triassic (early Anisian) Röt Formation of Waldhaus, southwestern Germany. Finally, we review the spatial and temporal distribution of the earliest archosaur fossils and their implications for understanding the dynamics of the archosaur radiation. Conclusions/Significance Comprehensive numerical phylogenetic analyses demonstrate that both Ctenosauriscus and the Waldhaus taxon are members of a monophyletic grouping of poposauroid archosaurs, Ctenosauriscidae, characterised by greatly elongated neural spines in the posterior cervical to anterior caudal vertebrae. The earliest archosaurs, including Ctenosauriscus, appear in the body fossil record just prior to the Olenekian/Anisian boundary (c. 248 Ma), less than 5 million years after the Permian–Triassic mass extinction. These earliest archosaur assemblages are dominated by ctenosauriscids, which were broadly distributed across northern Pangea and which appear to have been the first global radiation of archosaurs. PMID:22022431

Genomic instability in the epidermis induced by atomic bomb (A-bomb) radiation: a long-lasting health effect in A-bomb survivors.

PubMed

Naruke, Yuki; Nakashima, Masahiro; Suzuki, Keiji; Kondo, Hisayoshi; Hayashi, Tomayoshi; Soda, Midori; Sekine, Ichiro

2009-08-15

Radiation etiology is suggested in the occurrence of basal cell carcinoma (BCC) of the skin among atomic bomb (A-bomb) survivors. Any genotoxicity, including ionizing radiation, can induce a DNA damage response (DDR), leading to genomic instability (GIN), which allows the accumulation of mutations during tumorigenesis. In this study, the authors evaluated the presence of GIN in the epidermis of survivors as a late effect of A-bomb radiation. In total, 146 BCCs, including 23 cases arising from nonexposed skin, were identified in survivors from 1968 to 1999. The incidence rate (IR) of BCC was calculated with stratification by distance in kilometers from the hypocenter (< or =1.5 km, 1.6-2.9 km, and > or =3 km). Nineteen epidermal samples surrounding BCC at the nonexposed sites were collected and tested for p53 binding protein 1 (53BP1) expression with immunofluorescence. 53BP1 rapidly forms nuclear foci at the sites of DNA double strand breaks (DSBs). Because 1 manifestation of GIN is the induction of endogenous DSBs, the level of 53BP1-focus formation (DDR type) can be considered as a marker for GIN. : The incidence rate of BCC increased significantly as exposure distance approached the hypocenter. Of the 7 epidermal samples from the proximal group (< or =1.5 km), 5 samples predominantly expressed DDR and an abnormal type of 53BP1 expression. In contrast, 4 of 5 samples from the distal group (> or =3 km) and all samples from the control group predominantly expressed the stable type of 53BP1 expression in the epidermis. : The current results demonstrated the endogenous activation of DDR in the epidermis surrounding BCC in the proximal group, suggesting the presence of a GIN in the survivors as a late effect of A-bomb radiation, which may indicate a predisposition to cancer.

Space radiation-associated lung injury in a murine model.

PubMed

Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Schweitzer, Kelly S; Berdyshev, Evgeny V; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S; Yu, Yongjia; Globus, Ruth K; Solomides, Charalambos C; Ullrich, Robert L; Petrache, Irina

2015-03-01

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions. Copyright © 2015 the American Physiological Society.

Multicenter Study of Carbon-Ion Radiation Therapy for Mucosal Melanoma of the Head and Neck: Subanalysis of the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS) Study (1402 HN).

PubMed

Koto, Masashi; Demizu, Yusuke; Saitoh, Jun-Ichi; Suefuji, Hiroaki; Tsuji, Hiroshi; Okimoto, Tomoaki; Ohno, Tatsuya; Shioyama, Yoshiyuki; Takagi, Ryo; Nemoto, Kenji; Nakano, Takashi; Kamada, Tadashi

2017-04-01

To evaluate the efficacy and safety of carbon-ion radiation therapy (RT) for mucosal melanoma of the head and neck (MMHN) in the Japan Carbon-Ion Radiation Oncology Study Group study. Patients with MMHN with N0-1M0 status who were treated with carbon-ion RT at 4 institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. Two hundred sixty patients (male, 111; female, 149; median age, 68 years) with histologically proven MMHN were enrolled. Primary sites included the nasal cavity in 178 patients, paranasal sinuses in 43, oral cavity in 27, and pharynx in 12. Eighty-six patients had T3 tumors, 147 had T4a tumors, and 27 had T4b tumors. Two hundred fifty-one patients were diagnosed with N0 disease, and 9 with N1 disease. The median total dose and number of fractions were 57.6 Gy RBE (relative biological effectiveness) and 16, respectively. Chemotherapy including dimethyl traizeno imidazole carboxamide was used concurrently in 129 patients. The median follow-up duration was 22 months (range, 1-132 months). The 2-year overall survival and local control rates were 69.4% and 83.9%, respectively. Multivariate analysis showed that gross tumor volume and concurrent chemotherapy were significant prognostic factors for overall survival. Grade 3 and grade 4 late morbidities were observed in 27 and 7 patients (5 developed ipsilateral blindness, 1 mucosal ulcer, and 1 second malignant disease in the irradiated volume), respectively. No patients developed grade 5 late morbidities. Carbon-ion RT is a promising treatment option for MMHN. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Information retrieval from black holes

NASA Astrophysics Data System (ADS)

Lochan, Kinjalk; Chakraborty, Sumanta; Padmanabhan, T.

2016-08-01

It is generally believed that, when matter collapses to form a black hole, the complete information about the initial state of the matter cannot be retrieved by future asymptotic observers, through local measurements. This is contrary to the expectation from a unitary evolution in quantum theory and leads to (a version of) the black hole information paradox. Classically, nothing else, apart from mass, charge, and angular momentum is expected to be revealed to such asymptotic observers after the formation of a black hole. Semiclassically, black holes evaporate after their formation through the Hawking radiation. The dominant part of the radiation is expected to be thermal and hence one cannot know anything about the initial data from the resultant radiation. However, there can be sources of distortions which make the radiation nonthermal. Although the distortions are not strong enough to make the evolution unitary, these distortions carry some part of information regarding the in-state. In this work, we show how one can decipher the information about the in-state of the field from these distortions. We show that the distortions of a particular kind—which we call nonvacuum distortions—can be used to fully reconstruct the initial data. The asymptotic observer can do this operationally by measuring certain well-defined observables of the quantum field at late times. We demonstrate that a general class of in-states encode all their information content in the correlation of late time out-going modes. Further, using a 1 +1 dimensional dilatonic black hole model to accommodate backreaction self-consistently, we show that observers can also infer and track the information content about the initial data, during the course of evaporation, unambiguously. Implications of such information extraction are discussed.

Multicenter Study of Carbon-Ion Radiation Therapy for Mucosal Melanoma of the Head and Neck: Subanalysis of the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS) Study (1402 HN)

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

Koto, Masashi, E-mail: koto.masashi@qst.go.jp; Demizu, Yusuke; Saitoh, Jun-ichi

Purpose: To evaluate the efficacy and safety of carbon-ion radiation therapy (RT) for mucosal melanoma of the head and neck (MMHN) in the Japan Carbon-Ion Radiation Oncology Study Group study. Methods and Materials: Patients with MMHN with N0-1M0 status who were treated with carbon-ion RT at 4 institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. Two hundred sixty patients (male, 111; female, 149; median age, 68 years) with histologically proven MMHN were enrolled. Results: Primary sites included the nasal cavity in 178 patients, paranasal sinuses in 43, oral cavity in 27, and pharynx in 12. Eighty-six patients hadmore » T3 tumors, 147 had T4a tumors, and 27 had T4b tumors. Two hundred fifty-one patients were diagnosed with N0 disease, and 9 with N1 disease. The median total dose and number of fractions were 57.6 Gy RBE (relative biological effectiveness) and 16, respectively. Chemotherapy including dimethyl traizeno imidazole carboxamide was used concurrently in 129 patients. The median follow-up duration was 22 months (range, 1-132 months). The 2-year overall survival and local control rates were 69.4% and 83.9%, respectively. Multivariate analysis showed that gross tumor volume and concurrent chemotherapy were significant prognostic factors for overall survival. Grade 3 and grade 4 late morbidities were observed in 27 and 7 patients (5 developed ipsilateral blindness, 1 mucosal ulcer, and 1 second malignant disease in the irradiated volume), respectively. No patients developed grade 5 late morbidities. Conclusion: Carbon-ion RT is a promising treatment option for MMHN.« less

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

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

Bishop, Andrew J.; Greenfield, Brad; Mahajan, Anita

2014-10-01

Purpose: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity. Methods and Materials: We reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity. Results: At 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742;more » nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction. Conclusions: Survival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function.« less

A Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Mesalamine Suppositories 1 g at Bedtime and 500 mg Twice Daily in Patients with Active Mild-to-Moderate Ulcerative Proctitis

PubMed Central

2010-01-01

Abstract Background Ulcerative proctitis (UP) is a prevalent condition associated with increased morbidity and mortality. Topical mesalamine (5-aminosalicylic acid [5-ASA]) inhibits inflammatory processes in UP. Methods We evaluated effects of mesalamine 1-g suppository administered QHS compared with 500-mg suppository administered BID on UP activity (e.g., disease extension/mucosal appearance), remission, onset of response, safety and compliance in 97 patients with UP. A 6-week, randomized, multicenter, parallel-group, noninferiority study was conducted (and published) with Disease Activity Index (DAI) at week 6 as the primary efficacy variable and individual components of DAI at week 6 (i.e., stool frequency, rectal bleeding, mucosal appearance, global assessment) as secondary variables. Unreported outcomes were remission (DAI < 3 at weeks 3 and 6), disease extension, and complete response to treatment (DAI = 0; post-hoc, exploratory analysis). Results DAI values after 6 weeks were significantly reduced (±SD) from 6.6 ± 1.5 to 1.6 ± 2.3 (500-mg BID); and from 6.1 ± 1.5 to 1.3 ± 2.2 (1-g QHS). Mucosal appearance significantly improved from baseline after 3 and 6 weeks of treatment from 1.8 ± 0.5 to 0.8 ± 0.7 and 0.5 ± 0.7 (500-mg BID; P ≤ 0.0062) and from 1.7 ± 0.5 to 0.9 ± 0.5 and 0.4 ± 0.6 (1-g QHS; P ≤ 0.0001), respectively. Remission was comparable (78.3–86.1%); onset of response generally occurred within 3 weeks, and disease extension was reduced (>70%) after 6 weeks in both groups. Mesalamine was well tolerated. Compliance was >96%. Conclusions Mesalamine 500-mg BID and 1-g QHS suppositories are safe and effective for patients with UP. Most patients reported significant improvement within 3 weeks and UP remission and reduced disease extension after 6 weeks of treatment. Validity of QHS administration was confirmed. PMID:20676771

Evaluation of enterochromaffin cells and melatonin secretion exponents in ulcerative colitis

PubMed Central

Chojnacki, Cezary; Wiśniewska-Jarosińska, Maria; Kulig, Grażyna; Majsterek, Ireneusz; Reiter, Russel J; Chojnacki, Jan

2013-01-01

AIM: To study an assessment of the number of enterochromaffin cells and expression of hydroxyindole-O-methyltransferase in colonic mucosa and urine excretion of 6-sulfatoxymelatonin in patients with ulcerative colitis. METHODS: The study included 30 healthy subjects (group I-C), 30 patients with ulcerative proctitis [group II-ulcerative proctitis (UP)] and 30 patients with ulcerative colitis [group III-ulcerative colitis (UC)] in acute phases of these diseases. The number of enterochromaffin cells (EC) was estimated in rectal and colonic mucosa. Bioptates were assembled from many different parts of the large intestine. Immunorective cells collected from various parts of the colon were counted according to the Eurovision DAKO (Dako A/S, Copenhagen, Denmark) System in the range of 10 fields in each bioptate at × 200 magnification. The level of mRNA expression of hydroxyindole-O-methyltransferase (HIOMT) in colonic mucosa was estimated with RT-PCR. Urine 6-sulfatoxymelatonin (6-HMS) excretion was determined immunoenzymatically using an IBL (IBL International GmbH, Hamburg, Germany) kit (RE 54031). RESULTS: The number of EC cells in healthy subjects (C) was 132.40 ± 31.26. In patients of group II (UP) and group III (UC) the number of these cells was higher - 225.40 ± 37.35 (P < 0.001) and - 225.24 ± 40.50 (P < 0.001) respectively. Similar differences were related to HIOMT expression, which was 1.04 ± 0.36 in group C, 1.56 ± 0.56 (P < 0.01) in group UP and 2.00 ± 0.35 (P < 0.001) in group UC. Twenty-four hour 6-HMS urinary excretion was as follows: C - 16.32 ± 4.95 μg/24 h, UP - 26.30 ± 7.29 μg/24 h (P < 0.01), UC - 42.30 ± 12.56 μg/24h (P < 0.001). A correlation between number of EC cells and 6-HMS excretion was noted in all groups: r = 0.766 in patients with UP, r = 0.703 with UC and r = 0.8551 in the control group; the correlation between the results is statistically significant. CONCLUSION: In the acute phases of both UP and UC, proliferation of EC cells and high expression of HIOMT and urine excretion of 6-HMS is noted. These changes may represent a beneficial response in the anti-inflammatory and defense mechanism. PMID:23801861

Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

PubMed

Price, Jeremy G; Stone, Nelson N; Stock, Richard G

2013-08-01

To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

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

Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G., E-mail: Richard.Stock@mountsinai.org

2013-08-01

Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, andmore » treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT.« less

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

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

Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the targetmore » volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.« less

Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation Exposure

NASA Technical Reports Server (NTRS)

Maes, Olivier C.; Xu, Suying; Hada, Megumi; Wu, Honglu; Wang, Eugenia

2007-01-01

Exposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2 Gy suggest the cellular response to functionally suppress the apoptotic death signaling reflex after exposure to high dose radiation. Further analyses with transcriptome and global proteomic profiling will validate the reciprocal expression of signature microRNAs selected in our radiation-exposed cells, and their candidate target gene families, and test our hypothesis that unique radiation-specific microRNAs are keys in governing signaling responses for damage control of this environmental hazard.

Image Accumulation in Pixel Detector Gated by Late External Trigger Signal and its Application in Imaging Activation Analysis

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

Jakubek, J.; Cejnarova, A.; Platkevic, M.

Single quantum counting pixel detectors of Medipix type are starting to be used in various radiographic applications. Compared to standard devices for digital imaging (such as CCDs or CMOS sensors) they present significant advantages: direct conversion of radiation to electric signal, energy sensitivity, noiseless image integration, unlimited dynamic range, absolute linearity. In this article we describe usage of the pixel device TimePix for image accumulation gated by late trigger signal. Demonstration of the technique is given on imaging coincidence instrumental neutron activation analysis (Imaging CINAA). This method allows one to determine concentration and distribution of certain preselected element in anmore » inspected sample.« less

Simple Method to Estimate Mean Heart Dose From Hodgkin Lymphoma Radiation Therapy According to Simulation X-Rays

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

Nimwegen, Frederika A. van; Cutter, David J.; Oxford Cancer Centre, Oxford University Hospitals NHS Trust, Oxford

Purpose: To describe a new method to estimate the mean heart dose for Hodgkin lymphoma patients treated several decades ago, using delineation of the heart on radiation therapy simulation X-rays. Mean heart dose is an important predictor for late cardiovascular complications after Hodgkin lymphoma (HL) treatment. For patients treated before the era of computed tomography (CT)-based radiotherapy planning, retrospective estimation of radiation dose to the heart can be labor intensive. Methods and Materials: Patients for whom cardiac radiation doses had previously been estimated by reconstruction of individual treatments on representative CT data sets were selected at random from a case–controlmore » study of 5-year Hodgkin lymphoma survivors (n=289). For 42 patients, cardiac contours were outlined on each patient's simulation X-ray by 4 different raters, and the mean heart dose was estimated as the percentage of the cardiac contour within the radiation field multiplied by the prescribed mediastinal dose and divided by a correction factor obtained by comparison with individual CT-based dosimetry. Results: According to the simulation X-ray method, the medians of the mean heart doses obtained from the cardiac contours outlined by the 4 raters were 30 Gy, 30 Gy, 31 Gy, and 31 Gy, respectively, following prescribed mediastinal doses of 25-42 Gy. The absolute-agreement intraclass correlation coefficient was 0.93 (95% confidence interval 0.85-0.97), indicating excellent agreement. Mean heart dose was 30.4 Gy with the simulation X-ray method, versus 30.2 Gy with the representative CT-based dosimetry, and the between-method absolute-agreement intraclass correlation coefficient was 0.87 (95% confidence interval 0.80-0.95), indicating good agreement between the two methods. Conclusion: Estimating mean heart dose from radiation therapy simulation X-rays is reproducible and fast, takes individual anatomy into account, and yields results comparable to the labor-intensive representative CT-based method. This simpler method may produce a meaningful measure of mean heart dose for use in studies of late cardiac complications.« less

A Novel MiRNA-Based Predictive Model for Biochemical Failure Following Post-Prostatectomy Salvage Radiation Therapy

PubMed Central

Stegmaier, Petra; Drendel, Vanessa; Mo, Xiaokui; Ling, Stella; Fabian, Denise; Manring, Isabel; Jilg, Cordula A.; Schultze-Seemann, Wolfgang; McNulty, Maureen; Zynger, Debra L.; Martin, Douglas; White, Julia; Werner, Martin; Grosu, Anca L.; Chakravarti, Arnab

2015-01-01

Purpose To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy. Methods Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence. Results Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone. Conclusion miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies. PMID:25760964

Late Consequential Surgical Bed Soft Tissue Necrosis in Advanced Oropharyngeal Squamous Cell Carcinomas Treated With Transoral Robotic Surgery and Postoperative Radiation Therapy

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

Lukens, J. Nicholas; Lin, Alexander, E-mail: alexander.lin@uphs.upenn.edu; Gamerman, Victoria

Purpose: A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC) managed with transoral robotic surgery (TORS) and postoperative radiation therapy (PORT) developed soft tissue necrosis (STN) in the surgical bed months after completion of PORT. We investigated the frequency and risk factors. Materials and Methods: This retrospective analysis included 170 consecutive OP-SCC patients treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up. STN was defined as ulceration of the surgical bed >6 weeks after completion of PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. Results: A total of 47 of 170 patients (28%) hadmore » a diagnosis of STN. Tonsillar patients were more susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of 66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0-5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy, respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median time to STN was 2.5 months after PORT. All patients had resolution of STN after a median of 3.7 months. Multivariate analysis identified tonsillar primary (odds ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8% (2 of 26 patients) experienced STN (all grade 2). Conclusions: A subset of OP-SCC patients treated with TORS and PORT are at risk for developing late consequential surgical bed STN. Risk factors include tonsillar location, depth of resection, radiation dose to the surgical bed, and severe mucositis. STN risk is significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day to the surgical bed.« less

Simple method to estimate mean heart dose from Hodgkin lymphoma radiation therapy according to simulation X-rays.

PubMed

van Nimwegen, Frederika A; Cutter, David J; Schaapveld, Michael; Rutten, Annemarieke; Kooijman, Karen; Krol, Augustinus D G; Janus, Cécile P M; Darby, Sarah C; van Leeuwen, Flora E; Aleman, Berthe M P

2015-05-01

To describe a new method to estimate the mean heart dose for Hodgkin lymphoma patients treated several decades ago, using delineation of the heart on radiation therapy simulation X-rays. Mean heart dose is an important predictor for late cardiovascular complications after Hodgkin lymphoma (HL) treatment. For patients treated before the era of computed tomography (CT)-based radiotherapy planning, retrospective estimation of radiation dose to the heart can be labor intensive. Patients for whom cardiac radiation doses had previously been estimated by reconstruction of individual treatments on representative CT data sets were selected at random from a case-control study of 5-year Hodgkin lymphoma survivors (n=289). For 42 patients, cardiac contours were outlined on each patient's simulation X-ray by 4 different raters, and the mean heart dose was estimated as the percentage of the cardiac contour within the radiation field multiplied by the prescribed mediastinal dose and divided by a correction factor obtained by comparison with individual CT-based dosimetry. According to the simulation X-ray method, the medians of the mean heart doses obtained from the cardiac contours outlined by the 4 raters were 30 Gy, 30 Gy, 31 Gy, and 31 Gy, respectively, following prescribed mediastinal doses of 25-42 Gy. The absolute-agreement intraclass correlation coefficient was 0.93 (95% confidence interval 0.85-0.97), indicating excellent agreement. Mean heart dose was 30.4 Gy with the simulation X-ray method, versus 30.2 Gy with the representative CT-based dosimetry, and the between-method absolute-agreement intraclass correlation coefficient was 0.87 (95% confidence interval 0.80-0.95), indicating good agreement between the two methods. Estimating mean heart dose from radiation therapy simulation X-rays is reproducible and fast, takes individual anatomy into account, and yields results comparable to the labor-intensive representative CT-based method. This simpler method may produce a meaningful measure of mean heart dose for use in studies of late cardiac complications. Copyright © 2015 Elsevier Inc. All rights reserved.

'Full dose' reirradiation of human cervical spinal cord.

PubMed

Ryu, S; Gorty, S; Kazee, A M; Bogart, J; Hahn, S S; Dalal, P S; Chung, C T; Sagerman, R H

2000-02-01

With the progress of modern multimodality cancer treatment, retreatment of late recurrences or second tumors became more commonly encountered in management of patients with cancer. Spinal cord retreatment with radiation is a common problem in this regard. Because radiation myelopathy may result in functional deficits, many oncologists are concerned about radiation-induced myelopathy when retreating tumors located within or immediately adjacent to the previous radiation portal. The treatment decision is complicated because it requires a pertinent assessment of prognostic factors with and without reirradiation, radiobiologic estimation of recovery of occult spinal cord damage from the previous treatment, as well as interactions because of multimodality treatment. Recent studies regarding reirradiation of spinal cord in animals using limb paralysis as an endpoint have shown substantial and almost complete recovery of spinal cord injury after a sufficient time after the initial radiotherapy. We report a case of "full" dose reirradiation of the entire cervical spinal cord in a patient who has not developed clinically detectable radiation-induced myelopathy on long-term follow-up of 17 years after the first radiotherapy and 5 years after the second radiotherapy.

Radiation protection issues in galactic cosmic ray risk assessment

NASA Technical Reports Server (NTRS)

Sinclair, W. K.

1994-01-01

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.