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R Smith

Publications and source records attributed to R Smith.

At least 739 records · Page 41Linked to original sources
PubMed1993

Management at the MRC.

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Institutional Management Teams↗
PubMed1993

Monoclonal antibody imaging in patients with colorectal cancer and increasing levels of serum carcinoembryonic antigen. Experience with ZCE-025 and IMMU-4 monoclonal antibodies and proposed directions for clinical trials.

In an effort to identify the site of recurrent colorectal cancer in patients with occult metastasis and increasing serum CEA levels, we conducted two trials using monoclonal antibodies (MoAb) against CEA. The first utilized Indium-111-labeled ZCE-025; an immunoglobulin G1 (IgG1) anticarcinoembryonic antigen (anti-CEA) antibody (Hybritech, San Diego, CA). The second study used Tc-99m-labeled Fab' fragment of IMMU-4 (Immunomedics, Morris Plains, NJ). Eighteen patients were imaged with the ZCE-025 and 14 with the Tc-99m Fab' IMMU-4. True-positive scans, defined as at least one correct correlation of the MoAb scan and surgical/histologic findings, were observed in 12 of 15 patients undergoing exploration or biopsy using the ZCE-025 and 11 of 14 using the IMMU-4. There were no true-negative scans with the ZCE-025 and only 2 of 14 with the IMMU-4. There were 3 false-positive scans with the ZCE-025 and 1 of 14 with IMMU-4. There were no false-negative scans with either ZCE-025 or IMMU-4. Four (31%) of 13 patients undergoing exploration and imaged with ZCE-025 and 5 (36%) of 14 imaged with IMMU-4 had complete tumor resection. Treatment decisions were affected in 3 (16%) of 18 ZCE-025-imaged patients and 3 (21%) of 14 IMMU-4 ones. Two (14%) of 14 patients imaged with IMMU-4 had negative MoAb scans and negative laparotomies. Despite these findings, it is not known whether such early detection and resection will translate into improved survival rates. The authors suggest two randomized studies, one designed to ascertain the role of MoAb added to blind exploratory laparotomy. In that study, patients with increasing CEA levels and a negative workup will be randomized to an exploratory laparotomy preceded by MoAb anti-CEA scans or a straight exploratory laparotomy without the assistance of a MoAb anti-CEA scan. Endpoints will be differences in complete resectability and survival. A second study will examine the merits of blind exploratory laparotomies. In that study, patients with increasing CEA levels and a negative workup would be randomized to MoAb imaging, exploratory laparotomy, and radioimmunoguided surgery, and the other cohort of patients would continue to have conventional radiologic workup. Exploration in this latter group would be performed only when indicated by radiologic or endoscopic studies. The endpoint of the study would compare survival in the two cohorts of patients. These two studies may ultimately settle the debate regarding the correct approach to patients with occult metastatic colorectal cancer and a increasing levels of serum CEA.

Antibodies, Monoclonal↗
PubMed1993

Born to be boss.

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Administrative Personnel↗
PubMed1993

Identification of T- and B-cell epitopes associated with a restricted component of the Epstein-Barr virus-induced early antigen complex.

Experiments were designed in an attempt to identify T- and B-cell epitopes expressed on the 17-kDa early-antigen-restricted (EA-R) polypeptide of the EBV-induced early antigen complex. Using Berzofsky's algorithm, 3 hypothetical T-cell epitopes on p17 were synthesized and employed in EBV-specific lymphoproliferative assays. Lymphocytes from all EBV-infected donors responded against one of these epitopes (p17.1) irrespective of their serological status relative to antibodies to EA-R. Both CD4+ and CD8+ T-cell subpopulations from seropositive donors proliferated in the presence of p17.1 in short-term cultures. These experiments therefore identified one T-cell epitope on the 17-kDa polypeptide. In contrast, sera from anti-Ea antibody-positive individuals reacted with all 3 synthetic peptides to varying degrees, with p17.1 being the most frequently reactive epitope. When the sera were grouped according to diagnosis, it was noted that 82% of the sera from patients with aggressive lymphomas, whether Africans with Burkitt's lymphoma or North Americans with intermediate-grade large-cell or high-grade B-cell lymphoma, contained antibody reactive with p17.1, while 64% were reactive with p17.2 and 29% with p17.3. In contrast, high anti-EA antibody-positive sera from nasopharyngeal carcinoma patients were relatively less reactive with these synthetic peptides (23% positive with p17.1; 19% with p17.2; and 13% with p17.3). These results therefore identified 3 B-cell EA-R epitopes which might be potentially useful for clinical or epidemiological studies of EBV-associated lymphoproliferative diseases.

Amino Acid Sequence↗
PubMed1993

Chaotropic anion-phosphatidylcholine membrane interactions: an ultra high field NMR study.

NMR studies on the interaction of the linear chaotropic anions, SCN- and SeCN-, with sonicated egg phosphatidylcholine (EPC) vesicles have been carried out at field strengths up to 14.1 Tesla. At 600 MHz, both anions cause splitting or increased splitting of the choline N+(CH3)3, CH2N+ and O3POCH2 1H resonances with SeCN- being somewhat more effective in this action than is SCN-. No changes were observed in the glycerol CH2OP and CH2OCO 1H resonances and the phosphate 31P resonance of the headgroup region. The 13C spectrum was unchanged by the presence of the anions. After 18 h of exposure to the anion, the 1H resonance splittings but not the chemical shift values returned to those prior to anion exposure. Increasing the temperature of the vesicles decreased the anion-induced splitting, but, upon return to the beginning temperature, the chemical shifts did not return to their original values. The results are considered in terms of the 'molecular electrometer' model recently developed by Seelig and co-workers [1].

Liposomes↗
PubMed1993

Measuring utility values for QALYs: two methodological issues.

Two methodological concerns in utility estimation, the development of health state descriptions (scenarios) and the interpretation of interval scale anchor points, are examined in the context of disease-specific cost utility analyses (CUA). It is contended that results in CUA can be fundamentally biased by: (i) how the information presented in a scenario is generated; and (ii) the researcher's 'definition' of anchor points, when these are used as bounds to the interval scale. A number of recommendations are made, in particular for a more explicit reporting of these issues in CUA, to facilitate greater consistency in the application of utility measurement techniques.

Cost of Illness↗