Evaluation of refolding conditions for a recombinant human interleukin-3 variant (daniplestim).

The refolding of daniplestim, a human interleukin-3 variant (SC-55494) from Escherichia coli inclusion bodies, was optimized using a reversed-phase HPLC method developed to permit quantification of the reduced and oxidized forms of daniplestim. The presence of cysteine or dithiothreitol accelerated refolding of daniplestim from E. coli inclusion body slurries dissolved in urea or guanidine solutions and was complete in 4-6 h. Regardless of the dissolution and refolding protocol used to renature daniplestim, equivalently bioactive protein was produced. Under refolding conditions, no covalent modification of daniplestim by cysteine or cyanate was observed. The folding process was characterized further by following the unfolding of purified daniplestim by far-UV CD and fluorescence spectroscopies under both oxidizing and reducing conditions at pH values between 7 and 11. Formation of the single disulphide bond had a large stabilizing effect on daniplestim structure ( approximately 4-5 kCal at pH 9.5). This thermodynamic stabilization drove the refolding process towards the native form, even under conditions where the reduced protein was largely unfolded. From these data, scaleable refolding conditions for daniplestim were established.

Socioeconomic status, social environment, depression and postdischarge adjustment of the cardiac patient.

In this study, we assess the adjustment achieved by patients following discharge from coronary care and the role of socioeconomic status (SES), social environment (SE), and depression in achieving that adjustment. Two hundred eighty-seven patients were enrolled. The SE into which the patients were to be discharged was rated significantly poorer for patients of lower SES, who also scored higher on depression. At 1, 6, and 12 months postdischarge, lower SES patients recorded significantly poorer levels of adjustment across a range of functioning. Predischarge depression, together with measures of SE and SES, determined 10% to 28% of the variance in 12-month postdischarge adjustment. These data suggest the importance of identifying patients at greater risk for less than optimal outcome (those lower in SES and higher in depression), and the need to address the nature of the SE in which the patient has to effect his/her recovery.

End-of-life confusion in patients with cancer.

PURPOSE/OBJECTIVES: To review the literature on confusion at the end of life, provide accurate definitional and defining characteristics of confusion, and outline nursing strategies for its resolution. DATA SOURCES: Published articles, computerized databases, book chapters, reference lists from chapters and journal articles. DATA SYNTHESIS: As a major component of symptom distress in terminal care, confusion has not been defined clearly and therefore has not benefited from rigorous assessment and study as have other end-of-life symptoms. CONCLUSIONS: Increased knowledge about confusion that occurs in patients with widely metastatic cancer will assist in accurate symptom identification, early recognition, and timely management to reduce cognitive symptom distress at the end of life. Improved symptom resolution also can benefit family coping during terminal care. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can devise management protocols for confused patients that include screening criteria, pharmacologic interventions, environmental support, and prophylactic safety measures.

Lessons learned from clinical nurse specialist longevity.

This paper provides insight into issues related to longevity and retention of experienced clinical nurse specialists (CNS). To date, this phenomenon has received little attention in both clinical and administrative literature. To prepare for a national presentation on this component of advanced practice, the author questioned 12 professional colleagues who had practised in their role for over 10 years in the same setting. The CNS responses are described and critiqued and suggestions for support of veteran CNS are provided by the author.

Documentation and outcomes of advanced nursing practice.

PURPOSE/OBJECTIVES: To review literature related to documentation and evaluation of the competency of advanced practice nurses (APNs) and outline consensus findings specific to this area from the State-of-the-Knowledge Conference on Advanced Practice in Oncology Nursing. DATA SOURCES: Published articles in professional journals and written summations from the conference. DATA SYNTHESIS: Documentation and evaluation of APN competency is characterized by continued questioning about optimum approaches and methods. The literature to date has offered suggestions to initiate evaluation in APN practice. When documenting and evaluating APN competency, quality enhancement efforts and indices of cost-effectiveness must be considered. To expand APN practice opportunities, documentation and evaluation must be considered as a desired and necessary quantification of practice and not just as extra work. Efforts to promote this way of thinking will enhance marketability of the APN role in cancer care. CONCLUSION: Little research of APN outcomes exists. To counter this paucity, ONS and other organizations need to develop theoretical models to support outcomes documentation, which, in turn, enhances political and organizational savvy and promotes a viable future for APNs. NURSING IMPLICATIONS: Improved documentation of nursing interventions is required to justify the necessity and effectiveness of the APN role. In the ever-changing arena of health and cancer care, oncology APNs must ensure their positions in both existing and evolving marketplaces though efficient documentation and evaluation.

Vesicant extravasation: myths and realities.

PURPOSE/OBJECTIVES: To provide a comprehensive review of the literature pertinent to the phenomenon of antineoplastic vesicant extravasation within the framework of common misconceptions held by oncology nurses. DATA SOURCES: National guidelines, published articles in professional specialty journals and proceedings, and the authors' clinical experiences in the care of patients receiving vesicant agents. DATA SYNTHESIS: Antineoplastic vesicant extravasation can result in significant morbidity, severely limiting quality of life for patients with cancer. It also is a liability concern for oncology nurses. Many unanswered questions regarding extravasation exist because the phenomenon is difficult to study in humans and actual extravasation injuries are both sporadic and underreported. The incidence of extravasation from vascular access devices is unknown. Similarly, many recommended management strategies are empirically based. Misconceptions about the nature of extravasation injuries and the manner in which they should be managed contribute to poor patient outcomes and increased liability. CONCLUSIONS: The disproval of 10 myths regarding the nature and management of vesicant extravasation is an adjunctive step in the translation of existing national guidelines to workable institutional standards and appropriate professional practice. NURSING IMPLICATIONS: Oncology nurses are in a strategic position to observe the feasibility and efficacy of prevention and management guidelines established at national and local levels. Oncology nurses involved in the administration of antineoplastic vesicant agents are responsible for maintaining a current knowledge base about vesicants and for planning nursing care within the established standards of practice.

Realities to guide novel and necessary nursing care in geriatric oncology.

Recent acknowledgement of the prominence of cancer in the elderly has stimulated interest in this patient population at risk. Due to the newness of this interest, currently there is no formal recognized specialty of geriatric oncology that parallels pediatric oncology. However, there is growing concern and interest in identifying elder-specific indices of difficulty, disparity, and duty to optimize cancer prevention, control, therapy, support, and rehabilitation efforts for this growing population of aged patients. This article will provide a comprehensive review of relevant literature pertaining to nursing care of elderly adults who face cancer. Six realities to guide cancer nursing planning will be identified that address key patient-family-professional issues into the elder continuum.

New identities: the changing profile of patients with cancer, their families, and their professional caregivers.

PURPOSE/OBJECTIVES: To discuss and project cancer care needs and a vision of oncology nursing in the next century. DATA SOURCES: Scholarly, professional, and governmental sources of information. DATA SYNTHESIS: Projections of a changed patient/family profile, social support dilemmas, and a new "hybrid" oncology nurse. CONCLUSIONS: Opportunities for nurses, resulting from these projections, include roles as minority needs specialist, director of new care-delivery models, facilitator of intergenerational support teams, overseer of neighborhood-based care systems, multispecialty nursing care provider, cancer care policy activist. IMPLICATIONS FOR NURSING PRACTICE: Nursing education, community models, and current care-delivery settings will all be affected by the projected changes and will all need to consider adjusting to meet the demands that will be placed on them to facilitate change.

Cancer in the elderly: the forgotten priority.

In 1992, the American Oncology Nursing Society produced a state-of-the-art document, recognizing the fact that cancer is primarily a disease of ageing and addressing the specific needs of elderly cancer patients. As 1993 has been dubbed the 'Year of the Elderly', European oncology nurses should also be establishing a framework to meet the cancer-specific needs of the elderly.

Staffing in cardiology in the United Kingdom 1990. Sixth biennial survey: with data on facilities in cardiology in England and Wales 1989.

The Sixth Biennial Survey of Staffing in Cardiology was conducted in July 1990. This report summarises the data that were collected, together with the results of a survey of facilities in cardiology made in 1989. The total number of cardiologists in the United Kingdom, defined as individuals trained in the specialty and spending at least 40% of their time working in it, is now 323. Six individuals work part time only, making 320 whole time posts. This number has increased over the two years from 1988 to 1990 by 32, of which 23 work only in the specialty and nine as general physicians with a major interest in cardiology. The rate of increase in numbers over the past decade has been reasonably consistent with an average of approximately 4.4% per year. Thirty one districts in England and Wales still have no cardiologist and 13 other districts have little provision with an average of three (visiting) sessions each per week. The population in these 44 districts is 8.3 million. Scotland also has an inadequate distribution of service in the specialty. If recommendations for cardiac surgery and angioplasty made in the Fourth Report of a Joint Cardiology Committee of the Royal College of Physicians of London and the Royal College of Surgeons of England are to be met, we calculate that we need 63 more cardiologists in our major centres. To provide one cardiologist in every district hospital and two for larger districts would require 94 more specialists, making a total shortfall of 157 individuals. We have no excess of senior registrars to provide for a major expansion at consultant level. Time spent within the senior registrar (or academic equivalent) grade has tended steadily to decline and very few now reach the end of their contracts. The need for more individuals to pass through the senior registrar grade will be met in part by a planned reduction in the training period to three years. This will be inadequate, however, because projected retirements show that the number of consultant vacancies will increase sharply from 1997. We believe that additional senior registrar posts must be created if a serious shortfall in service provision by consultants is to be avoided. The provision of non-invasive facilities in cardiology is reasonable. The need for additional equipment for invasive cardiology has not been assessed. The number of physiological measurement technicians varies considerably between regions and is generally inadequate.

Characterization of human progesterone receptor by high performance hydrophobic interaction chromatography.

High performance hydrophobic interaction chromatography has been used to separate progestin receptors (PRs) from human uterus and from the T47D human breast cancer cell line. Reproducible separations of high resolution were achieved using a TSK Phenyl-5PW column and a reverse salt gradient of 400 mM to 0 mM sodium sulfate in phosphate buffer, pH 7.4. Peaks of radioactivity exhibiting hydrophobic behaviour were isolated, as well as a smaller proportion of specific bound receptors located in the void volume fraction. No differences in retention times were observed between uterine and breast cell line samples. When the technique was used in conjunction with rapid vertical tube sucrose density gradient centrifugation, the 8S sedimenting PR from fresh, low-salt cytosol always eluted with a retention time of 24 min. The natural 4S receptor chromatographed as a single peak at 29 min while the 4S receptor species from high-salt cytosol appeared as two distinct peaks of radioactivity with retention times of 29 and 33 min. While specific binding was shown to occur in the void volume of the column, the origin of these receptors were indeterminate. These results would suggest that under these conditions the 8S receptor occurs as a single hydrophobic class of protein, whereas the data provides evidence that transformed 4S receptor may be proportioned into two unequal entities as a function of exposure to salt.

Staffing in cardiology in the United Kingdom 1988. Fifth biennial survey.

This is the fifth survey of staffing (consultants and senior registrars) in cardiology in the United Kingdom. Data from previous years--including the fourth survey (1986) that was not published separately--are used to show the trends over the past decade. In 1988 there were less than six cardiologists per million population. The United Kingdom, with Ireland, has fewer cardiologists than all other European countries with reliable figures. The ratio for Europe as a whole is approximately 45 per million population; the recommended figure for the United States of America is 60 per million. The distribution of cardiologists in England and Wales is still very uneven. Seven million people--nearly 15% of the population--have no immediate access to special expertise in cardiology. Women are particularly poorly represented in the specialty. This survey indicates that the crisis in staffing for cardiology continues. It will worsen as the possibilities grow for effective management of heart disease and as needs increase with the greater average age of the population. Resolution of this crisis should be a major priority in policies aimed at countering the ravages of heart disease.

Discharge from a coronary care unit: psychological factors.

Anxiety is commonly experienced by patients following myocardial infarction. The role of anxiety in the recovery/rehabilitation process is not well understood, but anxiety is thought to be one of the factors determining outcome. It is important, therefore, to understand the possible effects on anxiety of changing discharge policies in coronary care units. Anxiety was assessed in a sample of MI patients, with good or poor prognoses, assigned to either early or late discharge from a coronary care unit. Although the overall level of anxiety of the total sample was not unduly high, it was clear that there was a subgroup of individuals, high in trait anxiety and with a poor prognosis, for whom early discharge was contra-indicated. Irrespective of prognosis, it was clear that early discharge did not produce a uniform response, indicating the need to differentiate between patients when determining the optimal date for discharge.