Biomedical subjects
J Reno
Publications and source records attributed to J Reno.
Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin's lymphoma (NHL): initial phase I/II study results.
Pretargeted radioimmunotherapy (PRIT) was investigated in patients with non-Hodgkin's lymphoma (NHL). The PRIT approach used in this study is a multi-step delivery system in which an antibody is used to target streptavidin to a tumor associated antigen receptor, and subsequently biotin is then used to target 90Y radioisotope to the tumor localized streptavidin. A chimeric, IgG1, anti-CD20 antibody, designated C2B8 or Rituximab, was conjugated to streptavidin (SA) and administered to patients with NHL. Thirty-four hours later, a clearing agent, synthetic biotin-N-acetyl-galactosamine, was administered to remove non-localized conjugate from the circulation. Finally, a DOTA-biotin ligand, labeled with 111In for imaging and/or 90Y for therapy was administered. Ten patients with relapsed or refractory NHL were studied. In three patients, the C2B8/SA conjugate was radiolabeled with a trace amount of 186Re in order to assess pharmacokinetics and biodistribution using gamma camera imaging. Seven patients received 30 or 50 mCi/m2 90Y DOTA-biotin. Re-186 C2B8/SA images confirmed that the conjugate localized to known tumor sites and that the clearing agent removed > 95% of the conjugate from the circulation. Radiolabeled biotin localized well to tumor. Unbound radiobiotin was rapidly excreted from the whole body and normal organs. The mean tumor dose calculated was 29 +/- 23 cGy/mCi 90Y and the average whole body dose was 0.76 +/- 0.3 cGy/mCi 90Y, resulting in a mean tumor to whole body dose ratio of 38:1. Only grade I/II non-hematologic toxicity was observed. Hematologic toxicity was also not severe; i.e., five of the seven patients who received 30 or 50 mCi/m2 of 90Y-DOTA-biotin experienced only transient grade III (but no grade IV) hematologic toxicity. Although six of ten patients developed humoral immune responses to the streptavidin, these were delayed and transient and hence may not preclude retreatment. Six of seven patients who received 30 or 50mCi/m2 90Y achieved objective tumor regression, including three complete and one partial response. The estimate of tumor to whole body dose ratio (38:1) achieved with PRIT in these NHL patients is higher than has been achieved in other studies using conventional RIT. Toxicity was mild and tumor response encouraging. PRIT clearly deserves additional study in patients with NHL.
Utilizing insider-outsider research teams in qualitative research.
Teams including members from both inside and outside the organization being studied make valuable contributions. A team configuration including both insiders and outsiders is highly effective because variations in the experience history of researchers on the team broaden the available perspectives and maximize the potential interpretations of observed behaviors. An insider-outsider research team consisting of university faculty and nurses at two psychiatric hospitals conducted a study, Meanings of State Hospital Nursing. This article summarizes the study, discusses issues to be resolved when using an insider-outsider research team, and presents the ways in which this approach enhanced the trustworthiness of our findings.
Mad about Metabolife.
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Meanings of state hospital nursing. I: Facing challenges.
The purpose of this study was to describe the meaning of work for nurses employed in two state psychiatric hospitals. Nurses at both hospitals participated in designing and carrying out the research. In Phase I, nurses described situations in which they had been observers or participant observers and the way that they understood what was occurring in the situations described. The data from these descriptions were analyzed in collaboration with small groups of nurse co-investigators at each hospital. In Phase II, patterns of meaning identified in Phase I were checked and further refined based on focus groups and interviews with nurses at both hospitals. The interrelated dilemmas faced by nurses are discussed as (1) challenges in clinical decision making, (2) challenges regarding personal control, and (3) challenges of maintaining professional standards. Ways of meeting these challenges, coping, and making meaning are discussed in a companion article, "Meanings of State Hospital Nursing II: Coping and Making Meaning".
Neuroimaging of vessel amyloid in Alzheimer's disease.
Despite extensive recent advances in understanding Alzheimer's disease (AD) we are unable to noninvasively establish a definite diagnosis during life and cannot monitor the cerebral deposition of amyloid beta protein (A beta) in living patients. We evaluated the use of 10H3, a monoclonal antibody Fab targeting A beta protein 1-28 labeled with Tc-99m. Six subjects with probable AD were studied using single-photon emission computed tomography (SPECT) at times from 0-24 hours following injection. Curves of radioactivity in blood demonstrate a half-life of the injected Fab of 2-3 hours. Images show uptake around the head in the scalp or bone marrow in all subjects. There is no evidence of cerebral uptake of the antibody. Scalp biopsies in all six patients demonstrate diffuse staining with 10H3 of the scalp, a pattern indistinguishable from that found in controls. Evidence of amyloid deposition in the scalp in AD is not seen with other anti-A beta antibodies, suggesting that 10H3 is cross-reacting with another protein. Further studies with anti-A beta antibodies will require longer-lived radionuclides to detect cerebral uptake at later times after injection to allow for complete clearance from the blood. Alternately, imaging using labeled A beta itself may provide a means for noninvasive targeting of cerebral amyloid.
X-ray photoemission from small mercury clusters on II-VI semiconductor surfaces.
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Clinical experience with Tc-99m labeled (N2S2) anti-melanoma antibody fragments and single photon emission computed tomography.
We evaluated the imaging capability of murine Tc-99m-labeled antimelanoma Fab fragments in 12 patients with clinical stage II and III melanoma. Tc-99m-NRX118.7 antimelanoma Fab fragment, 10.0 to 27.2 mCi (370-1, 006 MBq), was injected IV 30 min after irrelevant nonspecific intact antibody and 5 min after intact specific antibody were given. In all patients, whole-body scans and spot views were obtained. Single photon emission computed tomography (SPECT) was additionally performed in eight of the patients. The procedure was well tolerated, and 31 of 38 known foci of melanoma were detected (sensitivity, 82%). SPECT aided in detecting and better localizing lesions in the head, neck, and chest. The specificity of the technique was satisfactory when interpretation was performed with a knowledge of normal sites of accretion and excretion of technetium-99m activity such as the kidneys and gut. In several instances, lesions were discovered by means of the antibody scan before detection by other methods, and in two instances, the lack of visualization on antibody scan of a palpable mass correctly indicated that no melanoma was present in the mass. Scan results in three patients led to alterations in patient care; including preventing aggressive surgical and nonsurgical treatments. Although these data are encouraging, evaluation in additional patients will be essential to determine the clinical utility of this antibody scan in the management of patients with melanoma.