Search PubMed⌕ Search

Biomedical subjects

D R Fisher

Publications and source records attributed to D R Fisher.

At least 73 records · Page 4Linked to original sources
PubMed1991

WR2721 protection of bone marrow in 131I-labeled antibody therapy.

The use of phosphorothioate radioprotectors such as WR2721 in radioimmunotherapy is attractive because radiation delivered to tumors is usually separated in time from that delivered to the marrow and most normal organs, making protection of tumors of little consequence. However, to be effective radioprotectors must provide continuous protection against radiation of varying dose rates. To evaluate the potential of radioprotectors in radioimmunotherapy we treated normal mice with graded amounts of WR2721 in combination with an LD90/30 (26 MBq) of 131I-labeled antibody. A regimen of 15 doses of WR2721, 200 mg/kg prior to antibody infusion followed by 100 mg/kg ip every 4 h for a total of 72 h, was the maximum tolerated dosage schedule. With this schedule, treatment with radioprotectors failed to prolong survival or delay myelosuppression from the 131I-labeled antibody. In contrast, this regimen of radioprotector provided partial protection from a single treatment of 10 Gy total-body radiation given at 0.2 Gy/min. Protection 30 min after the final dose of WR2721 was greater than 3 h after the 14th dose (60 min prior to the final dose). These results suggest that the potential role of phosphorothioate radioprotectors in a radioimmunotherapy is limited because of the difficulty in achieving continuous protection with nontoxic amounts of drug and possibly because of a limited effect on low-dose-rate radiation.

Amifostine↗
PubMed1990

Magnetic resonance imaging of muscle tears.

Magnetic resonance scans were obtained on 17 patients with acute, subacute, or chronic muscle tears. These patients presented with complaints of persistent pain or a palpable mass. Magnetic resonance findings were characterized according to alterations in muscle shape and the presence of abnormal high signal within the injured muscle. These areas of high signal were noted on both T1-weighted and T2-weighted scans and were presumed to represent areas of intramuscular hemorrhage.

Accidents, Traffic↗
PubMed1990

Radiation effect in mouse skin: dose fractionation and wound healing.

Radiation induced dermal injury was measured by the gain in the physical strength of healing wounds in mouse skin. A sigmoid dose response for the inhibition of wound healing 14 days after surgery was found for single doses of X rays. The sparing of dermal damage from fractionation of the X-ray dose was quantified in terms of the alpha/beta ratio in the linear-quadratic (LQ) model, at a wide range of doses per fraction reaching as low as about 1 Gy. The fit and the appropriateness of the LQ model for the skin wound healing assay was examined with the use of the Fe-plot in which inverse total dose is plotted versus dose per fraction for wound strength isoeffects. The alpha/beta ratio of the skin was about 2.5 Gy (95% confidence of less than +/- 1 Gy) and was appropriate over a dose range of 1 Gy to about 8 Gy. The low alpha/beta value is typical for a late responding tissue. This assay, therefore, has the advantage of measuring and forecasting late radiation responses of the dermis within a short time after irradiation.

Animals↗
PubMed1990

Value of MR imaging in staging osteochondral lesions of the talus (osteochondritis dissecans): results in 14 patients.

Osteochondral lesions (osteochondritis dissecans) of the talus are common articular lesions that are usually traumatic in origin. Clinical management of these lesions is based on whether or not the fragments are attached. We studied the value of MR imaging in determining the stability of the osteochondral fragments. In 13 of 14 patients who had had correlative surgery, we accurately predicted the presence and extent of attachment of the fragment to the talus by performing preoperative MR imaging. The other patient had a false-positive diagnosis of a chondral fragment. All seven partially attached fragments had an irregular high-signal zone on T2-weighted images at the fragment/talar interface. The four unattached fragments had a complete ring of fluid surrounding the lesion. On the basis of these findings, we think MR of the ankle can be used to assess accurately talar osteochondral lesion stability and aid in clinical decision making.

Adolescent↗
PubMed1990

Osteochondritis dissecans of the knee: value of MR imaging in determining lesion stability and the presence of articular cartilage defects.

Osteochondritis dissecans is a lesion of articular surfaces that is of uncertain etiology. These lesions are seen on radiographs as a bony defect or fragmentation of the subchondral bone. A bony defect may be an actual surface hole or the defect may be filled with fibrous tissue or fibrocartilage. Similarly, the apparent bone fragments may be only partially attached so they are unstable and prone to displacement or they may be firmly attached with fibrous tissue. Knowledge of fragment stability and the presence of an articular cartilage defect is useful in deciding on treatment. This information cannot be determined on plain films or clinical examination. We correlated MR examinations with arthroscopic findings in 21 patients with osteochondritis dissecans of the knee to see if MR imaging could be used to predict lesion stability and articular cartilage defects. A high-signal interface between the lesion and the femur was used as evidence of lesion instability and was found in 15 lesions. One of these lesions was questionably stable at surgery; the remainder were unstable and partially attached. The other six patients had displaced fragments with large articular defects that were clearly visualized on the MR examinations. We conclude that MR imaging is useful in evaluating articular surface defects and lesion stability in patients with osteochondritis dissecans.

Adolescent↗
PubMed1990

Imaging and treatment of B-cell lymphoma.

Ten patients with non-Hodgkin's lymphoma have been evaluated as candidates for experimental radioimmunotherapy and five of those patients have been treated with a single high dose of iodine-131-(131I) labeled anti-pan B-cell antibodies. The evaluation protocol involved collecting biodistribution data by quantitation of gamma camera images and by tumor biopsy from trace labeled doses of antibody, to estimate the relative radiation dose delivered to normal organs and tumor sites. Each patient received up to three escalating mass doses (0.5 mg/kg, 2.5 mg/kg, and 10.0 mg/kg) of radioiodinated antibody for determination of the antibody amount that yielded the most favorable biodistribution for treatment. The millicuries of 131I-labeled to the optimal antibody dose for therapy was selected to deliver 1,000 rads (three patients) or 1,500 rads (two patients) to normal uninvolved organs. Because severe bone marrow toxicity was expected, all patients had their bone marrow cryopreserved prior to entry into the study. This report details the methods and results of quantitative imaging, biodistribution data collection, and absorbed radiation dose estimation in patients with lymphoma receiving high level radioimmunotherapy with 131I-labeled antibodies.

Antibodies, Monoclonal↗
PubMed1988

Long-term repair in vivo of colony-forming ability and chromosomal injury in X-irradiated mouse hepatocytes.

The radiosensitivity of mouse hepatocytes in vivo was measured in terms of clonogenicity or chromosome damage (micronucleus production). Within 24 h of irradiation there was a dose-dependent increase in clonogenicity (dose-modifying factor, DMF = 1.37 +/- 0.09) followed by long-term repair which resulted in a DMF of 3.49 +/- 0.23 at 11 months. Such repair also took place, but to a lesser extent, after the end of fractionated irradiation. Cell proliferation, measured by tritiated thymidine autoradiography, was insufficient to explain the long-term reduction in radiosensitivity in terms of a dose-dependent replacement of damaged cells. Although there was a reduction in the frequency of cells with micronuclei, postirradiation, the magnitude of this decrease was relatively small; the DMF for micronucleus-free cells at 11 months was only 1.49 +/- 0.25. Thus the long-term increase in clonogenicity can only partially be explained in terms of repair of chromosome injury, assessed by the production of micronuclei.

Animals↗
PubMed1988

Dose fractionation and hepatocyte clonogens: alpha/beta congruent to 1-2 Gy, and beta decreases with increasing delay before assay.

The sensitivity to X-ray dose fractionation was assessed for hepatocytes forming colonies in fat pads in mice. When the cells were assayed 1 day after the last irradiation the alpha/beta ratio was 1.0-1.6 depending on the method of analysis. The alpha/beta ratio describing the shape of the single-dose survival curve was much higher, and it did not predict the response to fractionation. When the assay was delayed for 10 months after the fractionated irradiation, the alpha/beta ratio was 1.9-2.1, and the beta component showed the greatest change with time. It is concluded that hepatocytes respond to dose fractionation in a manner expected of a late-responding tissue, even when the cells are assayed as early as 1 day after the last dose.

Animals↗
PubMed1987

Foot deformity in hereditary onycho-osteodysplasia.

A 30-year-old woman with hereditary onycho-osteodysplasia was examined. In addition to the classic tetrad of fingernail and toenail dysplasia, patellar aplasia, iliac horns, and radial head hypoplasia and dislocation, she also had scoliosis, proteinuria, and distinctive bilateral foot anomalies. The foot deformity consisted of a ball-and-socket ankle joint, valgus ankle, forefoot supination, and lateral subluxation at the tarsal-metatarsal joints. The literature showed that the radiographic findings of foot deformity in this dysplasia have never been reported in detail before. Evidence suggests that this distinctive pattern of deformity may be more common than previously appreciated.

Adult↗
PubMed1986

Direct analysis of quantal radiation response data.

A direct analysis is proposed for quantal (all-or-nothing) responses to fractionated radiation and endpoint-dilution assays of cell survival. As opposed to two-step methods such as the reciprocal-dose technique, in which ED50 values are first estimated for different fractionation schemes and then fit (as reciprocals) against dose per fraction, all raw data are included in a single maximum-likelihood treatment. The method accommodates variations such as short-interval fractionation regimens designed to determine tissue repair kinetics, tissue response to continuous exposures, and data obtained using endpoint-dilution assays of cell survival after fractionated doses. Monte-Carlo techniques were used to compare the direct and reciprocal-dose methods for analysis of small-scale and large-scale studies of response to fractionated doses. Both methods tended toward biased estimates in the analysis of the small-scale (3 fraction numbers) studies. The alpha/beta ratios showed less scatter when estimated by the direct method. Most important, the 95 per cent confidence intervals determined by the direct method were more appropriate than those determined by reciprocal-dose analysis, for which 18 per cent (small-scale study) or 8 per cent (large-scale study) of the confidence intervals did not include the 'true' value of alpha/beta.

Animals↗
PubMed1983

Barrett's esophagus complicating lye ingestion. Demonstration by pertechnetate scintigraphy.

Tc-99m pertechnetate scintigraphy was performed in a patient with Barrett's esophagus and a history of previous lye ingestion. Radionuclide uptake was present in the distal two-thirds of the esophagus and persisted after the drinking of water. This technique is simple and accurate and may be of significant benefit in determining the presence and extent of Barrett's esophagus, which carries an increased incidence of adenocarcinoma development. Examination of patients with chronic gastroesophageal reflux, using this technique, is advocated.

Barrett Esophagus↗
PubMed1983

Levels of 234U, 238U and 230Th in excreta of uranium mill crushermen.

Pacific Northwest Laboratory conducted a research program to measure uranium and thorium levels in excreta of uranium mill crushermen who are routinely exposed to airborne uranium ore dust. The purpose of this work was to determine whether 230Th was preferentially retained in the body over either 234U or 238U. Urine and fecal samples were obtained from 14 active crushermen with long histories of exposure to uranium ore dust, plus four retired crushermen and three control individuals for comparison. Radiochemical procedures were used to separate out the uranium and thorium fractions which were then electroplated on stainless steel discs and assayed by alpha spectrometry. Significantly greater activity levels of 234U and 238U were measured in both urine and fecal samples obtained from uranium mill crushermen, indicating that uranium in the inhaled ore dust was cleared from the body with a shorter biological half-time than the daughter product 230Th. The measurements also indicated that uranium and thorium separate in vivo and have distinctly different metabolic pathways and transfer rates in the body.

Alpha Particles↗
PubMed1982

The in vivo fate of a 211At labelled monoclonal antibody with known specificity in a murine system.

A monoclonal antibody reactive against the human transferrin receptor has been labelled with the alpha and X ray emitting isotope Astatine 211. The labelling procedure does not affect the ability of the product to bind to the transferrin receptor on the human leukemic cell line HL60. Using a direct binding assay, 211At labelled antibody can be specifically inhibited from binding to its target cells by excess unlabelled antibody. Furthermore, the binding inhibition demonstrated in this system correlates to enhanced clonogenic survival of these cells, indicating that very few atoms of 211At/cell are required for cell death. Data obtained from labelled antibody injected into mice show that the labelled product in serum retains the ability to bind to HL60 cells in vitro, although tissue distributions of the injected activity implies that some of the radiolabel is lost from the protein. Despite this loss of label, preliminary experiments on the localization of labelled antibody to HL60 cells growing s/c in nude mice show that tumor tissue has a higher specific activity than all other tissues, other than blood, after 12 hours. This suggests that further work on the nature of label degradation in vivo is warranted in the context of potential therapeutic and diagnostic studies.

Animals↗