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B Edwards

Publications and source records attributed to B Edwards.

At least 91 records · Page 5Linked to original sources

Skeletal localization of samarium-153 chelates: potential therapeutic bone agents.

A series of stable complexes of 153Sm has been produced using multidentate acetate and phosphonate ligands. Biodistribution studies in unanesthetized rats showed varying degrees of bone and soft-tissue uptake for these complexes. Of the complexes studied, [153Sm] ethylenediaminetetramethylenephosphonate (EDTMP) showed the best combination of high bone uptake, low nonosseous uptake, and rapid blood clearance which warranted its further investigation in rabbits. Rabbit studies confirmed the [153Sm]EDTMP results obtained in rats. Blood clearance in rabbits was found to be more rapid than [99mTc] methylene diphosphonate (MDP). Scintigraphic images were virtually indistinguishable from [99mTc]MDP images. Lesion/normal bone ratios were determined from digitized images obtained using a drill hole model and found to be approximately 17:1. Based on these excellent biodistribution characteristics, [153Sm] EDTMP could be therapeutically useful in treating metastatic bone cancer.

Animals↗

153Sm radiotherapeutic bone agents.

Samarium-153 is a radionuclide which can be produced in high yield by neutron irradiation and which has nuclear properties that make it attractive for use as a radiotherapeutic agent. Several phosphonate complexes of 153Sm were synthesized and characterized by electrophoresis and HPLC. A procedure based on cation exchange chromatography was developed for measuring complex yields. The complexes could be produced in yields greater than 99%, were anionic, and most exhibited a single HPLC peak.

Acetates↗

In vivo skeletal localization properties of 99mTc complexes of large phosphonate ligands.

Tetramethylenephosphonate derivatives of norborane (TPNB) and dicyclopentadiene (TPDCPD) were shown to readily form stable chelates with 99mTc that had high and selective bone uptake. The skeletal uptake and blood clearance properties of 99mTc-TPNB were similar to 99mTc-MDP in both rats and rabbits. This suggests additional studies to further evaluate 99mTc-TPNB or perhaps other large-organic based multidentate phosphonate ligands as potential bone imaging agents is warranted.

Animals↗

The relationship of arrhythmias to walking activity during mobilization after myocardial infarction.

The extent to which everyday walking activity is responsible for ventricular arrhythmias in the first 6 weeks after suspected myocardial infarction has been studied by simultaneous 24-hour recordings of electrocardiogram and walking activity. Forty-eight recordings from 46 patients were identified which contained couplets, ventricular tachycardia or R-on-T extrasystoles. In 24 recordings (50%) all the arrhythmias occurred whilst the patient was at rest and in a further four recordings there were fewer arrhythmias during activity than would have been expected by chance. Nineteen recordings (40%) contained arrhythmias which may have been induced by activity but in only three of these was the relationship definite. Clear evidence of arrhythmias precipitated by walking was found in only a minority of patients mobilizing after suspected myocardial infarction.

Activities of Daily Living↗

In vitro analysis of donor bone marrow following monoclonal antibody treatment for the prevention of acute graft versus host disease.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following bone marrow transplantation. The in vitro removal of the GVHD-causing T-lymphocytes from donor marrow is one approach which could control this complication. Treatment of the donor bone marrow with lectins and erythrocyte-forming rosette depletion, anti-T-cell antisera or monoclonal antibodies are methods currently being tested to accomplish this. CT-2 is an immunoglobulin monoclonal antibody specific for the T-cell erythrocyte-forming rosette receptor. Bone marrow from 23 consecutive donors was treated in vitro with CT-2 and complement, prior to infusion, as a potential means of controlling GVHD. Surface marker analysis using erythrocyte-forming rosetting, and OKT-3 and OKT-11 monoclonal antibodies on paired samples of treated and untreated marrow demonstrated a mean depletion to 1% of the original number of T-cells. Proliferative responses to alloantigens and mitogens as well as cytotoxic and natural killer cell function were tested and found to be markedly reduced. Despite these effects on T-lymphocytes, viable hematopoietic stem cell colonies were retained. Clinical results following the in vitro T-lymphocyte depletion of donor bone marrow for the 8 histocompatible and 15 nonhistocompatible bone marrow transplantation are reported. Prompt engraftment with minimal GVHD, despite no posttransplant GVHD prophylaxis, was seen in seven of the matched patients. In the nonhistocompatible bone marrow transplantation, failure of engraftment occurred in 11 patients. Grades III-IV GVHD were seen in two of the four patients that engrafted despite good T-lymphocyte depletion. No predictive correlation could be found between the in vitro analysis of marrow following CT-2 treatment and clinical outcome.

Acute Disease↗

Medulloblastoma metastatic to the marrow. Report of four cases and review of the literature.

Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally. The skeleton is the most common site of extraneural metastases, but metastases to the bone marrow can also occur. Four cases of medulloblastoma metastatic to the marrow are reported. In addition, 31 cases from the medical literature are reviewed. Clinical features include bone tenderness, cytopenias and elevated serum alkaline phosphatase and lactic dehydrogenase levels. Skeletal involvement, especially of the pelvic bones, is frequently seen radiographically. Weight loss, soft tissue masses and a requirement for blood transfusion are also associated features. Marrow biopsy specimens are characterized by the presence of a small cell tumor often with fibrosis, necrosis and osteoblastic activity. The symptomatic response to chemotherapy is rapid, but chemotherapy resistance appears quickly. Only 1 in 4 cases diagnosed antemortem in this review lived for more than a year. We conclude that marrow aspiration and biopsy are indicated in the evaluation of patients with medulloblastoma and may serve to diagnose the cause of cytopenias, to verify extraneural spread and to provide prognostic information.

Adult↗

Functional profile of the isolated uremic nephron: intrinsic adaptation of phosphate transport in the rabbit proximal tubule.

The maintenance of phosphate homeostasis in uremia appears to be governed both by parathyroid hormone (PTH) and by PTH-independent adaptations in renal tubular function. The relative contributions of these two mechanisms that control phosphate excretion by the diseased kidney have been difficult to define in intact animals. The present study was designed to examine the nature of the adaptation of phosphate handling by the proximal tubule of subtotally nephrectomized, uremic rabbits in vitro. Euparathyroid and hyperparathyroid uremic rabbits were studied. Tubular sensitivity to PTH was examined in vitro. The dose-response relationship between bath PTH concentration and inhibition of lumen-to-bath phosphate flux (Jp-lb) in isolated perfused proximal straight tubules (PSTs) revealed that PTH sensitivity was increased in the euparathyroid uremic rabbits and was decreased in hyperparathyroid uremic rabbits. The dose-response to dibutyryl cAMP was the same as normal in both uremic groups. These data strongly suggest the existence of a receptor-mediated adaptation in the effects of PTH on the uremic proximal tubule. In addition to an altered PTH-sensitivity the uremic PST also exhibited an alteration in the basal rate of phosphate transport studied in the presence of normal rabbit serum. Although net volume flux across the PST increased in both uremic groups as a possible consequence of hypertrophy, net phosphate flux per unit length was unchanged. Considering the increase of luminal area in these tubules, net phosphate flux per unit reabsorptive surface area was actually decreased. This dissociation is supportive of the existence of an intrinsic tubular adaptation which is independent of the size of the tubule per se. These studies indicate that there is an intrinsic adaptation of the basal rate of phosphate transport by the uremic rabbit proximal tubule and that the sensitivity of the tubule to PTH is altered. The data are strongly suggestive of an increase in the number of PTH receptors in the proximal tubule of the euparathyroid uremic rabbit and suggest that "down regulation" or persistent occupancy of these receptors occurs when hyperparathyroidism supervenes.

Adaptation, Physiological↗

Central nervous system involvement in American Burkitt's lymphoma.

Sixty-four patients with American Burkitt's lymphoma (AMBL) treated at the National Cancer Institute were reviewed to determine the frequency and characteristics of central nervous system (CNS) involvement. Patients with minimal or completely resected tumor never had CNS disease. Of the 45 patients with more extensive disease, 15 had CNS disease: nine presented with CNS disease, six of whom subsequently had recurrent CNS disease, and six developed CNS disease only at relapse. There was a significant association between CNS and bone-marrow disease at presentation. Therapy of CNS disease consisted of short courses of intrathecal chemotherapy with cytosine arabinoside and methotrexate. Cranial irradiation was given only to patients with CNS relapse. There are six long-term survivors (LTS) who have been disease free for four to six years post chemotherapy. Of these six LTS, three presented with CNS disease, two experienced isolated CNS relapse, and one had CNS disease both at presentation and at relapse. Three of the six LTS never received cranial irradiation. It is concluded that CNS involvement in AMBL can be effectively treated, and that long-term remission, which is probably cure, can be achieved.

Adolescent↗

Influence of the cytoskeleton on the expression of a mouse hepatitis virus (MHV-3) in peritoneal macrophages: acute and persistent infection.

The effects of anti-cytokinetic drugs on virus production, formation of syncytia, cell surface changes and lysosomal damage were examined during mouse hepatitis virus 3 (MHV-3) infection of mouse peritoneal macrophages. Colchicine and vinblastine caused no detectable effect on the infectious process. In the presence of cytochalasin B the acute, highly cytopathogenic interaction that MHV-3 establishes with macrophages was converted into one which persisted for several days. Under these conditions the cell surface changes induced by the infection were maintained unaltered but cell fusion was reduced and no significant lysosomal damage was detectable.

Animals↗