Alternative Modes Of Delivery Research Articles

Marking and gene expression by a lentivirus vector in transplanted human and nonhuman primate CD34(+) cells.

Recently, gene delivery vectors based on human immunodeficiency virus (HIV) have been developed as an alternative mode of gene delivery. These vectors have a number of advantages, particularly in regard to the ability to infect cells which are not actively dividing. However, the use of vectors based on human immunodeficiency virus raises a number of issues, not the least of which is safety; therefore, further characterization of marking and gene expression in different hematopoietic lineages in primate animal model systems is desirable. We use two animal model systems for gene therapy to test the efficiency of transduction and marking, as well as the safety of these vectors. The first utilizes the rhesus animal model for cytokine-mobilized autologous peripheral blood CD34(+) cell transplantation. The second uses the SCID-human (SCID-hu) thymus/liver chimeric graft animal model useful specifically for human T-lymphoid progenitor cell reconstitution. In the rhesus macaques, detectable levels of vector were observed in granulocytes, lymphocytes, monocytes, and, in one animal with the highest levels of marking, erythrocytes and platelets. In transplanted SCID-hu mice, we directly compared marking and gene expression of the lentivirus vector and a murine leukemia virus-derived vector in thymocytes. Marking was observed at comparable levels, but the lentivirus vector bearing an internal cytomegalovirus promoter expressed less efficiently than did the murine retroviral vector expressed from its own long terminal repeats. In assays for infectious HIV type 1 (HIV-1), no replication-competent HIV-1 was detected in either animal model system. Thus, these results indicate that while lentivirus vectors have no apparent deleterious effects and may have advantages over murine retroviral vectors, further study of the requirements for optimal use are warranted.

What’s Funny about Nursing?

The authors examine the topic of humour and argue that humour is needed as one of many skills within the nurse patient relationship. We advance the view that humour has been well researched as an agent of therapeutic value and as a communication tool which helps to relieve stress, but, to date is not used to its fullest potential and tends therefore to be underestimated in both general and psychiatric nursing areas.Humour has benefits for both the nurse and the patient having psychological benefits and a vast array of physiological advantages and is regarded by those who use it as a social lubricant acting as a positive in nurse patient relationships. We also argue that it is essential that nurses know when to use humour as timing and appropriateness is imperative in order for it to be most effective. Humour can be used in all areas of clinical nursing practice and may prove useful in being a reliable predictor over the course of a patient’s illness. The use of humour can help improve the nurse-patient relationship by initially breaking the ice between nurse and patient. This alternative mode of delivery can then be foundational to other areas of the nurse patient relationship such as self-disclosure, the enhancement of learning and relieving stress. Furthermore, it helps to facilitate and promote mutual health and well being for both the patient and the nurse.The usage of humour in psychiatric nurse settings is discussed and the benefits to both the patients and their staff are outlined as being of immense therapeutic value. The literature perhaps tends to skirt around these benefits some what, as psychiatry and laughter in partnership are not really considered important discursive topics.

Laboratory medicine in the United Kingdom: 1948–1998 and beyond

The National Health Service in the United Kingdom was created in 1948, effectively becoming the main provider of healthcare and funded by the government from taxation. By the late 1970’s, and despite many achievements, it was seen to be approaching a financial crisis. Radical reforms were introduced in the early 1990’s bringing in general management, a split between purchaser and provider, and competition. Whilst there has been a change of government more recently several of these initiatives have been retained, with the exception of competition (the internal market) which has been abandoned. There is now a much greater focus on the quality of care with increased clinical and financial accountability. Laboratory medicine (generally termed pathology in the United Kingdom) has evolved to meet the demands of more patients, reducing turnaround times, a greater repertoire of investigations and a continuing improvement in productivity. There is an increasing focus on improved dialogue between the laboratory and the clinician covering interpretation of results, audit of services and outcomes, research and development and continuous education in the pursuit of a high quality service. The major challenges for the future focus on alternative modes of delivery, on issues relating to staffing and on quality of service, in the face of an ever increasing demand.

Treatment strategies for medulloblastoma and primitive neuroectodermal tumors

Medulloblastoma and primitive neuroectodermal tumors (PNETs) are the most common malignant brain tumors in children. The concern for late sequelae of neuraxis irradiation and the obligation to improve disease-free survival in children who harbor malignant brain tumors has led to the additional provision of systemic chemotherapy to standard- and reduced-dose radiotherapy, as well as to the evaluation of alternate modes of radiotherapy delivery. Analysis of evidence has suggested that chemotherapy has an impact on length of survival in children with medulloblastoma and PNETs. The question remains as to whether chemotherapy combined with reduced-dose radiotherapy provides greater benefit than standard-dose radiotherapy alone, and which subset of children the treatment most benefits. Also unanswered is the question of whether chemotherapy can serve as the primary treatment in infants with these lesions. In an attempt to help answer these questions, the authors review the major chemotherapy and radiotherapy trials for newly diagnosed patients and those with recurrent medulloblastoma and PNETs.

Novel delivery systems for coagulation proteins.

Long-term haemophilia prophylaxis with clotting factors administered by alternative delivery modes requires stable liquid formulations of these factors. We developed an aqueous-formulated human coagulation factor IX (hCFIX) with in vitro half-life (T 1/2) of 6 weeks at 37 degrees C and 18 months at 4 degrees C. Upon bolus subcutaneous (s.c.) injection in animals, hCFIX had a bioavailability of up to 16% compared to intravenous (i.v.) dose. When delivered by s.c. implanted pumps, hCFIX attained > 2% of normal human levels in the animal plasma. Hydrogels of hCFIX in a chitosan derivative, N,O-carboxymethyl chitosan (NOCC), released hCFIX slowly in vitro, and when injected s.c., gave prolonged plasma levels over those obtained by bolus i.v. or s.c. injection. Freeze-dried human coagulation factor VIII (hCFVIII) formulated in non-aqueous solvents had in vitro T 1/2 up to 80 days at 37 degrees C.

Comparing Alternative Service Delivery Modes: Municipal Enterprises Require Special Consideration

ABSTRACT:An increasingly constrained fiscal environment and unrelenting citizen demands for services have cities searching for new ways to provide many needed services. Municipal enterprises require special consideration because they provide many advantages for cities. However, because they are separate municipal funds, an understanding of commonly used fund transfer mechanisms, such as payments in lieu of taxes or services in kind, is essential to making valid service provision comparisons. This study uses examples from a recent national survey of cities to explain and illustrate various means used by municipal enterprises to transfer revenue to, and from, other municipal funds. It also provides examples of how accurately accounting for the resultant revenue can significantly alter the results of the comparison process for five commonly used utility enterprises.

Unsolicited Bids for Government Functions

This article develops the case for designing a process to encourage and evaluate unsolicited bids for privatization or contracting out of government functions. The authors argue that conventional government procurement practices are unlikely to uncover or reveal all potentially desirable opportunities for privatization or contracting out, given informational constraints, search costs, and bureaucratic and political disincentives operating on public sector agents. Thus, there is a strong case for reversing the burden of initiative with respect to alternative modes of delivery of public goods or services. The article develops a private sector analogy for unsolicited bids for government functions

Professional Empowerment and Teaching Sociology to Health Care Professionals

The teaching of the social and behavioral sciences as disciplines within the education and training of health care professionals is a relatively new phenomenon in the United Kingdom. The push for their inclusion in medical, nursing, midwifery and radiography curricula is a consequence of major changes in the system and service of health care in Britain, which lent a greater urgency to the professionalization of these occupations. This, in turn, called for professional and educational validating bodies to fundamentally reorganize courses, to raise their academic level, and to encourage widespread research into learning styles, continuing professional development, and alternative educational delivery modes such as open and distance learning. In teaching sociology across a range of newly developed health care courses we have had to consider the dynamics of United Kingdom health care education that prompted their development. This paper is based on our experiences in designing, implementing, and evaluating such courses.

TRNA delivery systems for ribozymes.

The delivery and expression of hammerhead ribozymes to eukaryotic cells have largely been achieved using RNA polymerase II (pol II)-based promoters for transcription of ribozyme sequences. These constructs produce transcripts that are capped (5′-m7G) at the 5′-end and contain long tracts of adenine residues (i.e., are polyadenylated) at the 3′-end. Although there is a large body of literature ( that suggests the success of pol II-based ribozyme constructs in reducing target gene activity, several other studies have provided evidence for alternate modes of delivery. This chapter will review the methods for the use of RNA polymerase III-based delivery systems. In particular, it will focus on the use of tRNA molecules as delivery systems for hammerhead ribozymes.

Facilitating Professional Development Through the Study of Supervision and Institutional Change

ABSTRACT This paper addresses two questions: What is involved for teacher educators in bringing about significant professional development in experienced teachers through coursework? How can university coursework proposed through an alternative mode of delivery facilitate this?

Preferences of students with learning disabilities for alternative service delivery modes

ABSTRACT This study investigates the preferences of students with learning disabilities regarding the location in which they receive help and the person from whom to get help. The attitudes of students with learning disabilities towards school as a function of the time they spend in the mainstream and their characteristics were also investigated. Results of the structured interviews and survey statements of 150 students indicated that they preferred receiving extra help in the special education class from the special education teacher. Students’ preferences for setting or teacher were not related to age, sex, IQ or academic achievement level, nor to the time students spent in the mainstream. The students expressed a positive attitude towards school in general, and towards their teachers, their classmates and the schoolwork in particular.

Lymphokine gene therapy for cancer

The plethora of recombinant lymphokines that have recently become available has led to renewed hope for an immunotherapeutic solution to cancer. Many lymphokines, either singly or in combination, have already shown promise in animal trials and in preliminary human trials. Systemic lymphokine toxicity has been the major constraint on this type of therapy, often precluding the use of doses sufficient to induce tumour regression. To realize the therapeutic potential of recombinant lymphokines against cancer, alternative modes of delivery are needed which maximally stimulate local anti-tumour responses whilst causing minimal systemic toxicity. In this article, Stephen Russell proposes that tumour cell targeted lymphokine gene therapy would optimize lymphokine delivery. Some of the practical difficulties likely to be encountered with such an approach are also discussed.

Online numeric databases : four years later

Identifies seven major trends in business databases: concentration of players; convergence of database systems; growth of numeric databases; end-user access; alternative delivery modes; development of PC software and more gateways. Examines the changing role of information professionals, and outlines the major numeric/statistical business databases.

Ambulatory infusion pumps: a practical view at an alternative approach.

W ITH the movement in the health care system to decrease hospital costs, there has been a significant shift from hospital care to the home and ambulatory care setting. Alternative modes of delivery of chemotherapeutic agents have been developed that are readily adapted to the outpatient setting. The development of reliable microvolume infusion pumps and safe long-term intravenous (IV) access has led to the feasibility of continuous infusion of chemotherapeutic agents. Continuous infusion studies of bleomycin, cytosine arabinoside, and doxorubicin have demonstrated improvement in the therapeutic index. l The failure to cure most metastatic solid tumors is most commonly a result of intrinsic or acquired drug resistance.2,3 Ineffective drug dosing or scheduling may contribute substantially to ineffective therapy.4*5 Continuous infusion addresses these problems by allowing the escalation of drug dose to overcome apparent drug resistance,6 and improvement in the therapeutic drug index by altering the drug schedule.’ There are four means by which continuous infusions of chemotherapy can be potentially effective in cancer treatment. They are (1) the destruction of malignant cells by continuous drug exposure through all phases of the cell cycle, regardless of the length of the malignant cell cycle (which has been shown to vary from 55 to 88 hours in one study of seven patients with squamous cell cancers**9; (2) the increased effectiveness of drugs with short half-lives by ensuring exposure of malignant cells at the time of replication*O; (3) the increased length of drug exposure to the tumor cell membrane may also increase the effectiveness of the therapy; and (4) the incidence and severity of specific organ drug toxicities may be lessened.1’-14

Kaiser, HMOs, and the public interest: a conversation with James A. Vohs. Interview by John K. Iglehart.

Prologue: In the array of American health care enterprises, the Kaiser Permanente Medical Care Program is a unique breed of big business and community service. Spawned by industrialist Henry J. Kaiser and physician Sidney Garfield, the program evolved during World War II as an answer to the medical needs of Kaiser's shipyard workers. In the ensuing four decades, the nonprofit program has become the largest private direct-service health care corporation in the world. For the last eleven years, James A. Vohs has served as chief executive officer of Kaiser Foundation Health Plan, the management side of the program. The program's 5,000 physicians, whose leaders enjoy an equal voice in a delicately balanced decision-making structure, are organized in Permanente Medical Groups. Vohs has presided over Kaiser Permanente during an era when its enrolled membership has more than doubled and in which the program —after years of resistance—decided to become a truly national enterprise. Within and outside of the program, Vohs is viewed as a man of intelligence, decisiveness, and high moral purpose. But now Vohs and Kaiser Permanente stand at a new crossroads, facing serious challenges from aggressive for-profit HMOs and other alternative delivery modes, corporations that self-insure their workforces, and an increasingly efficient fee-for-service sector. In this intensely competitive climate, the program is having to examine the very philosophic tenets upon which it has long been based. The central question is, “Can Kaiser Permanente survive and continue to prosper in a climate perhaps best characterized as social Darwinism, without changing its operating principles?” In this rare interview, Vohs elaborates on this and related questions, discusses his misgivings about health care companies that live by their quarterly earning reports, and muses about the uncertain future.

Enhanced tumor metastases upon drug delivery in cross-linked albumin beads.

Growth of the murine hepatoma H6 was significantly suppressed by amiloride, a sodium influx inhibitor. Primary tumor growth inhibition was augmented by loading the drug into cross-linked albumin carriers, but lung metastases were enhanced. These results emphasize the importance of using metastatic tumor models when testing new drugs and/or alternative modes of drug delivery.

Is cost containment working?

Prologue: The nations hospitals are undergoing a period of turbulent changes as a consequence of multiple new pressures: Medicares prospective payment system, increasing efforts by physicians to maintain their patients in ambulatory, rather than inpatient, settings, and the aggressive promotion of alternative delivery modes. In this essay, professor Karen Davis, chairman of the Department of Health Policy and Management at The Johns Hopkins University School of Hygiene and Public Health, and her colleagues report that hospital costs have indeed moderated as a consequence of these new forces. The cost moderation has come as a consequence of a sharp decline in the admission of patients, particularly those under age sixty-five and decline in the length-of-stay of elderly hospital patients. The important question now, as the authors declare, is whether these recent utilization trends will continue, whether they will level off or begin to increase. Davis was, in essence, the Carter administrations health policy thinker during the years 1977-80. Gerard Anderson is an associate professor in Davis's department and was, himself, a regarded health policy analyst at the Department of Health and Human Services during the years 1978-1983. Steven Renn, an attorney, and Diane Rowland, who is responsible for long-term care issues on the staff of the U.S. House Energy and Commerce Subcommittee on Health and the Environment, are research associates at Hopkins' Department of Health Policy and Management. Carl Schramm is an associate professor at Hopkins' School of Hygiene and Public Health and director of its Center for Hospital Finance and Management Steinberg, a physician, is an assistant professor and a Henry J. Kaiser Family Foundation Faculty Scholar at the Hopkins' medical school.

Continuing Education: A Collaborative Effort

Continuing education in interior design has had a relatively short history. Professional organizations are still in the formative stages of developing their continuing education or professional development programs. Since AIA has had a longer involvement with continuing education for architects their successful program provides useful insights for interior design. When developing individual programs one concern is with identifying appropriate topics. Programs are currently being designed and developed by several sources. Program quality controls include following CCEU guidelines, providing financial compensation and initiating a review process. Successful program implementation needs to address problems of participation, promotion and economic considerations as well as alternate modes of program delivery. Collaborative continuing education efforts among interior design organizations is seen as an efficient and effective means to establish a clearinghouse of resources; to provide a basis for experimental programs; to initiate team efforts in developing, reviewing and sponsoring programs in the future; and to develop a tradition for life–long–learning.

Low-Melting Phenytoin Prodrugs as Alternative Oral Delivery Modes for Phenytoin: A Model for Other High-Melting Sparingly Water-Soluble Drugs

□ Phenytoin is a high-melting, weakly acidic, and sparingly water-soluble drug. Because of these physicochemical properties, phenytoin is subject to erratic bioavailability in a variety of dosage forms both in its acidic as well as sodium salt forms. A homologous series of 3-acyloxymethyl derivatives of phenytoin (acetyl through decanoyl) were synthesized and various physicochemical properties measured. The prodrugs were more readily soluble in various metabolizable glycerol esters such as tributyrin, trioctanoin, and triolein than phenytoin. The solubility of the prodrugs in the various organic vehicles studied was closely correlated to the melting point of the prodrug: the lower the melting point the greater the solubility. The cleavage rates of the prodrugs in plasma and tissue homogenates followed a parabolic relationship with chain length. The prodrug, 3-pentanoyloxymethyl-5,5-diphenylhydantoin when administered in tributyrin gave superior oral phenytoin bioavailability in rats when compared with sodium phenytoin administered as an aqueous solution.

Treatment of schizophrenic patients in their homes through a visiting nurse—some issues in the nurse's training

Treatment of schizophrenic patients within their communities and away from mental hospitals has been accepted all over the world. The more developed countries of the world have experimented with various models of community care for the mentally ill for over two decades (Langsley et al., 1969; Pasamanic et al., 1967; Goodacre et al., 1975; Test and Stein, 1976; Hogarty et al., 1974). However, in the developing countries, where mental illness still suffers from severe social stigma, and where public opinion is not very enlightened regarding causation and treatment of mental illness, the acceptance of a policy of community care has been a slow process. At present, most of the developing countries have realized that the enormous task of treating all their mentally ill patients by way of hospitalization through a psychiatrist seems an unattainable objective and that community care may offer the only feasible alternative (Kapur, 1975; Swift, 1972; Wintrob, 1972). World bodies such as the World Health Organization and the Commonwealth Foundation have been advocating community-based care, offered through mental health professionals and paramedical personnel, as a possible model of delivery of care. Various experiments have been carried out by workers in many of the developing countries, which may be suitable for their particular cultural milieu (Lambo, 1973; Vidyasagar, 1973; Schmidt, 1973). These efforts have been made out of necessity. As such, their emphasis has not been on evaluation-oriented design. In India, the paucity of psychiatrists and institutional treatment facilities necessitates the management of the patients within their own homes. The poor economic condition of the majority of the people precludes utilization of nursing homes. One therefore has to look for alternative modes of treatment delivery which may be more practical, culturally acceptable, economical to operate, and yet would be aimed at reaching a greater number of people. Training more nurses is more economical and feasible than training more