Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of 131I-labeled monoclonal antibody CC49 in breast cancer: a phase II trial.

Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-alpha could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1. 07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity.

Oncology nurses' knowledge, practice, and educational needs regarding cancer genetics.

This study evaluated oncology nurses' knowledge of cancer genetics and related topics, and identified current practice patterns and perceived educational needs in this area. A 54-item study questionnaire was mailed to a random sample of 1,200 Oncology Nursing Society (ONS) members and 75 members of the ONS-Cancer Genetics Special Interest Group; 656 (51%) of those eligible responded. After exclusions, we analyzed 573 responses. Most respondents were Caucasian, female, and worked in hospital or outpatient settings. Half were staff nurses and 8% specialized in cancer genetics. Respondents with higher levels of nursing education or with continuing education in cancer genetics, who worked in positions other than staff nurses, and whose primary practice area was cancer genetics had significantly higher mean scores overall on questions measuring knowledge of cancer genetics and related areas. Higher perceived educational needs to improve knowledge or practice related to cancer genetics at basic, intermediate or advanced levels were associated with all or some of the following variables: lower education; hospital/ outpatient or managed care/private practice settings; lack of continuing education in cancer genetics, and positions other than advanced practice nurses. Although nearly half of the respondents had received patient inquiries regarding cancer genetics, only 35% were aware of referral resources and 26% had made such referrals. These findings may be used to develop targeted educational approaches that prepare oncology nurses to incorporate cancer genetics into any level of practice.

Different effects involved in the interaction of saccades and the vestibulo-ocular reflex.

The accuracy of human goal-directed saccades during passive sinusoidal whole-body rotation is the same as that of normal saccades with the head still. Two mechanisms contribute to this accuracy: 1. There is an incomplete summation (70% on the average) of saccade and VOR velocities. 2. The duration of saccades during head rotation is lengthened if VOR and saccade velocities have the same direction, and is shortened if their direction is opposite. The latter finding supports the hypothesis that saccades are controlled by local feedback.

Investigation of the coxsackievirus B3 nonstructural proteins 2B, 2C, and 3AB: generation of specific polyclonal antisera and detection of replicating virus in infected tissue.

The coxsackievirus B3 (CVB3) nonstructural proteins 2B and 3AB were synthesized as beta-galactosidase fusion proteins in E. coli in order to generate specific polyclonal antisera. 2B and 3AB fusion proteins were purified by preparative SDS-polyacrylamide gel electrophoresis and inoculated into rabbits. Protein 2C-specific antiserum was produced using synthetic oligopeptides which were defined by computer based amino acid sequence analysis. Specificity of the generated antisera was analysed by immunoblotting, immunofluorescence, immunohistochemistry and immunoelectron microscopy. All antisera allowed specific detection of the viral proteins 2B, 2C, and 3AB in CVB3-infected cells as well as in myocardial and pancreatic tissue of CVB3-infected mice. In addition, the CVB3 2C-specific antiserum was shown to be highly cross-reactive with the analogous protein of other picornaviruses, including cardiotropic enterovirus serotypes such as coxsackievirus A9, coxsackievirus B (types 1-5), and echovirus 11. Moreover, the immunological detection of nonstructural proteins enables diagnosis of replicating virus in infected tissue. These results demonstrate that the generated antisera are valuable tools for diagnostic approaches. Furthermore, they may help to elucidate the role of the nonstructural proteins 2B, 2C, and 3AB in enteroviral replication and pathogenesis.

EPR and NMR spectroscopic studies of [MoL2(MeC identical to CMe)Cp]z (L = P-donor ligand, z = 0 and 1): fluxionality in a metal-alkyne redox pair.

Variable temperature NMR and EPR spectroscopic studies provide rates and activation parameters for alkyne rotation and oscillation, respectively, in the fluxional redox pair [Mo(P(OMe)3)2(MeC identical to CMe)Cp][BF4] (diamagnetic) and [Mo(P(OMe)3)2(MeC identical to CMe)Cp] (paramagnetic).

Emerging strategies in the management of cancer.

PURPOSE/OBJECTIVES: To review advances in understanding the biology of cancer that will lead to new prognostic indicators and approaches for treating cancer and its metastases and to explore the implications of these developments for oncology nurses. DATA SOURCES: Published papers, abstracts, research result, package inserts, books, and personal experience. DATA SYNTHESIS: Understanding is evolving that cancer is a genetic disease that occurs when a single cell and its progeny are remarkably changed by a series of genetic mutations. A new paradigm for managing cancer is emerging that is based on new prognostic indicators, intracellular and intercellular communication, and biologic control. Potential new therapeutic strategies include gene-directed therapy, control of cellular proliferation, exploitation of cell death, inhibition of metastasis, and reversal of multidrug resistance. Many of these therapies are only beginning to enter phase I/II clinical trials. CONCLUSIONS: With continued progress, doctors will be able to identify patients with the highest likelihood of experiencing recurrent or progressive disease and formulate therapeutic strategies specific for their disease and even for their individual genetic makeup. IMPLICATIONS FOR NURSING PRACTICE: To remain abreast of these new and increasingly sophisticated treatments, oncology nurses must be knowledgeable about cell and cancer biology, human genetics, the immune system, a how advances in these fields are forming the foundation for new therapies. Nurses with creativity and drive will continue to lead the way in developing management strategies for patients receiving these new therapies.

A new approach to managing chemotherapy-related anemia: nursing implications of epoetin alfa.

PURPOSE/OBJECTIVE: To review the role of epoetin alfa (recombinant human erythropoietin) in the treatment of chemotherapy-related anemia and the nursing management of patients receiving this form of therapy. DATA SOURCES: Published books, journal articles, and monographs as well as clinical experience. DATA SYNTHESIS: Anemia is a common problem for patients with cancer. Successful management of anemia associated with cancer chemotherapy can lead to improved quality of life for patients during therapy. CONCLUSIONS: The use of epoetin alfa to treat the anemia associated with cancer chemotherapy represents a viable new therapeutic alternative to the use of transfusions. Oncology nurses play an important role in shaping care strategies for patients receiving cancer therapy. IMPLICATIONS FOR NURSING PRACTICE: The nurse's role in assessment, administration, monitoring and patient education provides the foundation for effective management of patients receiving epoetin alfa therapy.

Oncology nurses' attitudes regarding voluntary, physician-assisted dying for competent, terminally ill patients.

Euthanasia and "voluntary dying" are among the most controversial issues involved in cancer care. The purpose of this descriptive study was to explore oncology nurses' attitudes about physician-assisted death (PAD) for competent, terminally ill adults who request this assistance. Questionnaires were sent to 2,000 randomly selected members of the Oncology Nursing Society. The questionnaires included demographic questions, four vignettes describing patient care situations and possible responses based on beliefs about PAD, and questions that explored awareness of organizations and legislation that promote legalization of PAD. The response rate was 61% (1,210). Findings indicate that oncology nurses hold diverse views regarding the acceptability of PAD. Although many nurses favored PAD, they also expressed a reluctance to administer the medication that would cause death. Given that PAD is an ethical and legal issue in the United States for terminally ill patients, nurses are encouraged to become informed about the concept of PAD and be prepared to actively respond to the policy-making ramifications of the assisted-death movement.

Recent advances in the management of biotherapy-related side effects: fatigue.

Limited information about fatigue patterns in patients with cancer exists in the biotherapy literature. When fatigue is mentioned, it is usually to state whether or not it was a dose-limiting side effect. No further data are provided on how fatigue was measured; which patterns were noted and when; and which relationships were found between fatigue and demographic characteristics, type of biologic response modifier, route of administration, or cumulative dose. Thus, there is little available in the biotherapy literature to guide nursing practice in managing this side effect. Theory that guides practice, however, often emanates from the personal experiences of the patients and from the clinical observations and intuitive hunches of the nurses and physicians participating in clinical trials. These individuals have been most generous in sharing their insights and unpublished data with the authors. This paper presents a comprehensive view of current knowledge on fatigue to guide present nursing practice with patients receiving biotherapy and to provide direction for future nursing and clinical trial research.

Future projections in biotherapy.

OBJECTIVES: To review barriers to effective biotherapy and future trends in biotherapy and the expertise needed by oncology nurses to address the challenges that will result from these changes. DATA SOURCES: Review articles and book chapters related to biotherapy. CONCLUSIONS: To sustain the progress made in biotherapy, barriers that limit the effectiveness of treatment must be addressed and basic research continued. Targeted areas for new biotherapy strategies are interference with cellular communication, control of the cell cycle, and interference with the process of metastasis. IMPLICATIONS FOR NURSING PRACTICE: Nurses with creativity and motivation will continue to lead the way in developing management strategies for patients receiving future therapies.

Genetic testing and informed consent.

OBJECTIVES: To discuss unique issues related to cancer predisposition genetic testing and informed consent. DATA SOURCES: Published professional articles, review articles, research articles, clinical practice, position statements, websites, and textbooks. CONCLUSIONS: The discovery of germline mutations that confer a predisposition for the development of cancer will continue. The provision of adequate information is central to the process of genetic counseling and testing so that individuals may give informed consent and make choices appropriate to their own specific circumstances. IMPLICATIONS FOR NURSING PRACTICE: The use of genetic information for the management of cancer will impact the practice of all oncology nurses in the coming years. Knowledge of genes that predispose for cancer and standards that delineate essential components of quality care during the informed consent process is vital.

Recent advances in immunotherapy and monoclonal antibody treatment of cancer.

OBJECTIVES: To review the immune response and tumor immunology, and to provide an update on the success and obstacles to targeted therapy using monoclonal antibodies and antibody conjugates. DATA SOURCES: Research articles and textbooks. CONCLUSIONS: Ongoing studies are exploiting the targeting properties of the immune system to improve anticancer therapy. Both monoclonal antibodies and immunoconjugates have shown promise in treatment of specific diseases. IMPLICATIONS FOR NURSING PRACTICE: The rapid growth of molecular techniques has allowed for the development of new anticancer therapies. Since nurses are intimately involved in the delivery of such therapy as well as in educating patients regarding risks and benefits, they must be knowledgeable.

[One general pattern in the development of pathologic processes in the heart in various types of myocardial involvement]. / Ob odnoi obshchei zakonomernosti razvitiia patologicheskikh protsessov v serdtse pri razlichnykh tipakh porazheniia miokarda.

Experiments on 50 rabbits were made to study left and right ventricular function and ultrastructure of the heart in its diffuse and focal disease, overload of the intact heart. In the middle stage of the above conditions there was a distinct dyscoordination of the heart function and the growth of differences in the heart ventricles ultrastructures. This phenomenon may underlie the rise of intracardiac and general hemodynamic disturbances.

[Changes in myocardial ultrastructure in diphtheria intoxication]. / Dinamika ul'trastruktur miokarda pri difteriinoi intoksikatsii.

A drastic discoordination in the left and right ventricular ultrastructures was observed 72 hours after diphtheria toxin given to rabbits with experimental diphtheria intoxication. This may cause cardiac death in diphtheria intoxication.