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By: David Bruce Bartlett, PhD

  • Assistant Professor in Medicine
  • Member of the Duke Cancer Institute
  • Member of Duke Molecular Physiology Institute

https://medicine.duke.edu/faculty/david-bruce-bartlett-phd

Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation arthritis relief for dogs australia cheap indocin 25mg on line. Attenuation of radiation-induced genomic instability by free radical scavengers and cellular proliferation arthritis gene generic 50 mg indocin overnight delivery. Radiationinduced genomic instability: delayed mutagenic and cytogenetic effects of x rays and alpha particles arthritis in dogs surgery discount indocin 25 mg online. Comparison of the risks of cancer incidence and mortality following radiation therapy for benign and malignant disease with the cancer risks observed in the Japanese A-bomb survivors arthritis in distal joint of fingers cheap indocin 75mg on-line. Comments on the paper: Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors. Curvilinearity in the dose-response curve for cancer in Japanese atomic bomb survivors. Further analysis, incorporating assessment of the robustness of risks of cancer mortality in the National Registry for Radiation Workers. Describing time and age variations in the risk of radiation-induced solid tumour incidence in the Japanese atomic bomb survivors using generalized relative and absolute risk models. Relative risks of radiation-associated cancer: comparison of second cancer in therapeutically irradiated populations with the Japanese atomic bomb survivors. Chromosomal aberrations induced by plasma from irradiated patients: an indirect effect of x radiation. Cellular and molecular basis of the stimulator effect of lowdose radiation on immunity. Health examination and chromosome aberration analysis of residents living in 60Co-contaminated rebar buildings. Children of Chernobyl cleanup workers do not show elevated rates of mutations in minisatellite alleles. Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of x-rays. Chromosome instability as a result of double-strand breaks near telomeres in mouse embryonic stem cells. Screening for codon 249 p53 mutation in lung cancer associated with domestic radon exposure. Mortality of radiologists and pathologists in the Radiation Registry of Physicians. Instability of microsatellites in radiation-associated thyroid tumours with short latency periods. Mortality of workers at a nuclear materials production plant at Oak Ridge, Tennessee, 1947-1990. Effects of longcontinued total-body gamma irradiation on mice, guinea pigs, and rabbits. Effects on life span, weight, blood picture, and carcinogenesis and the role of the intensity of radiation. Dose and dose-rate dependence of the frequency of hprt deficient T lymphocytes in the spleen of the 137Cs gamma-irradiated mouse. Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation. Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation. Influence of dose rate on the induction of simple and complex chromosome exchanges by gamma rays. Twostage model of radon-induced malignant lung tumors in rats: effects of cell killing. Biologically based analysis of the data for the Colorado uranium miners cohort: age, dose and dose-rate effects. Breast cancer risk after radiotherapy in infancy: a pooled analysis of two Swedish cohorts of 17,202 infants. Somatic genetic events linked to the Apc locus in intestinal adenomas of the Min mouse. Estimate of cancer risk for a large population continuously exposed to higher background radiation in Yangjiang, China.

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In individuals with such susceptibility ecotrin arthritis relief 75mg indocin free shipping, the probability of developing a tumor during their lifetime can exceed 50% arthritis in back diagnosis 25 mg indocin for sale, and in some instances the probability is higher arthritis pain dogs cheap indocin 50mg without a prescription. The prevalence of currently known arthritis medication names indocin 25mg generic, high penetrance genes account for approximately 5% of the total cancers in the population, and the prevalence of such genes in the total population is less than 1%. Because of this incidence, it is difficult to obtain adequate data to assess the impact of such genes on susceptibility to radiation-induced cancer. Studies to date have demonstrated increased risks for radiation-induced osteosarcoma and soft tissue sarcoma in patients with the hereditary form of retinoblastoma. This hypothesis has been difficult to definitively test, and the question of enhanced susceptibility remains unresolved. A major area of uncertainty and increasing interest is the potential impact of low-penetrance mutations that are likely to be relatively common in the population. Experimental studies in animal models and in human cells have provided evidence for such mutations and provided data implicating such mutations in susceptibility to radiation-induced cancer. It is also likely that such low-penetrance mutations could be involved in other delayed effects, such as radiation-induced fibrosis. The identification of such susceptible subpopulations is now a major research activity in radiation oncology. Studies of such populations can provide information on the nature of potential risks and suggest new approaches to treatment that may reduce risks. Several studies have now been reported on risks of second cancers from radiation therapy. Data also are becoming available regarding risks of second cancers after whole body irradiation for bone marrow transplantations. Relatively little information has been reported on radiation-induced second cancers in long-term survivors of childhood cancer. Another complicating factor is that many of these patients received chemotherapeutic agents as well. Furthermore, in many cases insufficient time has passed for risks for adult solid tumors to be properly assessed. The most common second cancers appear after treatment of childhood cancers appears to be bone and soft tissue sarcomas. Although genetic susceptibility of these children to the familial form of these cancers can complicate interpretation, studies of retinoblastoma patients who do not have the familial form and studies of patients with other forms of childhood cancer also show increased risks for these sarcomas. Not unexpectedly, based on the earlier discussion about age susceptibility (see Age, earlier in this chapter), the risk for thyroid, breast, and skin cancers also are elevated after radiation therapy for a variety of childhood cancers, as are tumors of the central nervous system and leukemias. The relative increase in risk for leukemia development after radiation therapy is lower than that for the development of a subsequent solid cancer. A series of large studies have examined the development of second cancers in cervical cancer patients treated with high doses of ionizing radiation. The reason for such a small increase in leukemia risk is likely a result of a number of factors. First, the high doses delivered to a small volume likely resulted in cell killing in nearby target cells, and the dose outside the field was relatively low so that the fraction of target cell irradiated may have been small. In spite of the small numbers of leukemias, a dose-response curve was constructed that showed a rise in leukemia risk up to approximately 4 Gy, followed by a decline from the peak at higher doses. This decline at higher doses was suggested to be a result of cell killing that could have reduced the number of transformed cells. With respect to time of occurrence, a minimum latent period of approximately 2 years was seen, and the risk remained elevated for approximately 15 years before declining to normal levels. Within the field of irradiation, cancers of the bladder and bone, as well as soft tissue sarcomas, were observed. Outside of this field, cancers of the stomach were seen, probably as a result of scatter radiation of approximately 1 Gy. Radiation in combination with chemotherapeutic agents does not seem to markedly enhance the risk of leukemia over that associated with chemotherapy alone. For those treated between the ages of 15 and 24, the relative risk was 19; for ages 25 to 29 years, a relative risk of 7.

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The 2002 text by Order and Donaldson supplies several references arthritis otc meds indocin 50 mg overnight delivery, each with few cases to arthritis knee exercises pdf generic indocin 50 mg on-line report arthritis pain versus muscle pain cheap 75 mg indocin with visa, and mainly of mandible or maxillary origin zeel arthritis pain relief tablets generic indocin 50 mg with amex. Angiofibroma of nasopharynx (juvenile nasopharyngeal angiofibroma) While optimum management is controversial, there is general agreement that surgery is preferred if considered safe, as in cases when there is no extension into the orbital apex or base of skull. Since the typical patient is young, regard for the long-term hazard of radiation is important. When radiation is used, the radiation dose is lower than in malignant tumors of the same location. Policy: Radiation therapy is medically necessary in those cases with extension into the orbital apex or base of skull. Angiomatosis retinae (von Hippel Lindau syndrome) Capillary hemangiomas associated with von Hippel Lindau syndrome may be single or multiple, and can severely affect vision. Ankylosing spondylitis the use of radiation therapy in the treatment of ankylosing spondylitis is of historical interest. The risk of radiation-induced cancer and other morbidity contraindicates its use and is often cited as a common example of radiation carcinogenesis in radiobiological studies. Anovulation the use of radiation therapy in the treatment of anovulation is of historical interest only and is occasionally discussed in the treatment of functional pituitary adenomas. Arachnoiditis In the pre-antibiotic era the beneficial use of radiation for the treatment of arachnoiditis was described. Resolution is slow and may take years, during which the risk of hemorrhage is not eliminated. Arthritis (see total lymphoid irradiation for radioimmunosuppression) (see rheumatoid arthritis) (see osteoarthritis) N. Basalioma this synonym for basal cell carcinoma of the skin is sometimes included in lists of "benign" disorders of skin suitable for treatment with radiation therapy. It can be mistaken for other disorders because of the features it shares with psoriasis and eczema. Policy: Cases will require medical review and documentation that no other reasonable alternative exists. Bursitis, synovitis, and tendinitis Randomized studies in 1952, 1970, and 1975 cited in the Order and Donaldson review claimed "no benefit" to the use of radiation therapy for any of these, and the authors of the review recommend against its use. Department of Health, Education, and Welfare survey report of 1977 reporting the results of a survey of American radiation oncologists included these diagnoses as acceptable for treatment, as did the German survey of 2008. There is support in modern era texts, concluding that the use of radiation "may provide an alternative to conventional conservative treatment for patients who are not surgical candidates" (PerezBrady). Typical treatment is with photon beam therapy using, at most, complex treatment planning in five or fewer fractions. The presentation and behavior ranges from truly benign to aggressive with metastatic potential. Surgical resection has historically been the treatment of choice with radiation reserved for technically or medically inoperable cases. Precise histologic classification may help discriminate those truly benign lesions that would not be expected to benefit from radiation therapy from lesions that would be best treated as invasive carcinomas. For those unresectable non-secretory lesions causing symptoms such as pain, radiation may be beneficial. For secreting tumors, radiation therapy is limited to those causing symptoms that are not controllable by medical means. The relationship to subsequent malignant lymphoma is unclear, with malignant lymphoma reported in as many as 30% of cases. Synonyms include giant follicular lymph node hyperplasia, follicular lymphoreticuloma, angiomatous lymphoid hamartoma, and giant benign lymphoma. Low dose radiation therapy has been reported as effective in refractory or relapsed cases if further use of steroids is contraindicated. Castration There is evidence that with sufficient dose radiation can effectively and permanently cease gamete production and hormone production in the testes and ovaries. Surveys reported by Order and Donaldson (1998) indicated 75% of surveyed radiation oncologists would use radiation for this purpose with the appropriate indication. Department of Health, Education, and Welfare survey report of 1977 included castration as an acceptable indication.

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In the postoperative setting with negative margins rheumatoid arthritis ulnar deviation purchase indocin 75 mg with visa, 54 Gy in 30 fractions may be appropriate arthritis medication in kenya buy discount indocin 50 mg on-line. External beam photon radiation therapy arthritis medication with coumadin buy indocin 50 mg low cost, palliative In previously un-irradiated individuals with unresectable metastatic disease and symptomatic local disease or near obstructing primaries who have reasonable life expectancy arthritis guitar cheap indocin 25mg free shipping, external beam photon radiation therapy may be appropriate. Overview In the United States, the incidence of skin cancers outnumbers all other cancers combined, and basal cell cancers are twice as common as squamous cell skin cancers. While the two types share many characteristics, risk factors for local recurrence and for regional or distant metastases differ somewhat. Both types tend to occur in skin exposed to sunlight, and share the head and neck region as the area having the greatest risk for recurrence. Both occur more frequently and be more aggressive in immunocompromised transplant patients. In general, it is the squamous cell cancers that tend to be more aggressive, with a greater propensity to metastasize or to recur locoregionally. Anatomic location plays a role in risk stratification and is broken down into: "L" areas (trunk and extremities, excluding pretibia, hands, feet, nail units, ankles); "M" areas (cheeks, forehead, scalp, neck, pretibial); "H" areas (mask areas of face, including central face, eyelids, eyebrows, periorbital skin, lips, chin, overlying mandible, preauricular and postauricular skin, temple, ears, genitalia, hands, feet). Factors identified as placing the patient at increased risk for recurrence for basal and squamous cell skin cancers are included in Table 1. Management Treatment should be customized, taking into account specific factors and also patient preferences. The primary goal is to completely remove the tumor and to maximize functional and cosmetic preservation. Radiation therapy may be selected when cosmetic or functional outcome with surgery is expected to be inferior. In very low risk, superficial cancers, topical agents may be sufficient and cautiously used. When surgery is utilized, margin assessment using Mohs micrographic technique should include examining vertical sections of the specimen to assess deep margin and stage/depth of invasion. Photon and/or electron beam techniques are medically necessary for the treatment of basal cell and squamous cell cancers of the skin for any of the following: a. Definitive treatment for a cancer in a cosmetically significant location in which surgery would be disfiguring b. Adequate surgical margins have not been achieved and further resection is not possible c. Definitive management of large cancers as an alternative to major resection requiring significant plastic repair d. Definitive, preoperative, or postoperative adjuvant therapy for a cancers at risk for local or regional recurrence due to perineural, lymphovascular invasion, and/or metastatic adenopathy f. Radiation therapy should not be used in genetic conditions which predispose to skin cancer, such as xeroderma pigmentosum or basal cell nevus syndrome. Radiation treatments should be avoided or only used with great caution in cases of connective tissue disorders 2. When brachytherapy is required for treatment of skin cancers, up to ten (10) sessions is considered medically necessary. The beam energy and hardness (filtration) dictate the maximum thickness of a lesion that may be treated with this technique. Higher-energy external electron beam teletherapy (4 megaelectron volt [MeV] and greater) is most commonly utilized to treat the majority of localized lesions. Photon external beam teletherapy is required in circumstances in which other beams of lower energy are inadequate to reach the target depth. In the great majority of cases, simple appositional Complex technique is required, accompanied by lead, cerrobend, or other beam-shaping cutouts applied in the path of the beam and/or on the skin surface to match the shape of the target lesion. In complicated cases, such as when regional adenopathy or perineural invasion is present, more complicated techniques may be medically necessary. Treatment schedules with photons and/or electrons should be matched to the clinical circumstance, including size and depth of the lesion, histology, cosmetic goal, and risk of damage to underlying structures. Radiation doses typically range from 35 Gy in fractions of 7 Gy over 5 days, to 66 Gy in 33 fractions of 2 Gy over six and one-half weeks. The margin around tumor is typically different for basal and squamous histologies and for technique used (electrons, photons, superficial radiation). The radiation prescription is to be made by a qualified radiation oncologist who is familiar with the nuances of the dose deposition that accompany the physical characteristics of the radiation beams and techniques. Dose prescription for electrons is at the 90% isodose line, and for superficial or orthovoltage radiation at the Dmax.

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