Spatial and temporal expression of herpes simplex virus type 1 amplicon-encoded genes: implications for their use as immunization vectors

There is great interest in developing new immunization vectors. Helper virus-free herpes amplicons, plasmid-based vectors that encode no viral gene products and have an extremely large coding capacity, are attractive viral vaccine candidates for expressing recombinant proteins in vivo for immunization. Earlier studies in mice, using amplicons encoding the gp120 protein of human immunodeficiency virus (HIV), resulted in strikingly robust cellular immune responses as measured by cytotoxicity and interferon gamma enzyme-linked immunospot assays. To begin to understand how such vectors function in vivo to generate an immune response, we used amplicons encoding reporter constructs including green fluorescent protein (GFP) and luciferase to examine the duration of expression after administration to mice. Luciferase expression, measured with the IVIS system from Xenogen/Caliper Life Sciences (Hopkinton, MA) and by enzymatic assays of tissue extracts, revealed that expression after injection of the HSVluc amplicons peaked earlier than 24 hr after injection into mice. HSVegfp injection resulted in peak accumulation of GFP 24 hr after administration in vivo. Thus, both reporter genes revealed a rather rapid and robust expression pattern of short duration. The short period of expression appears in part to be due to gene silencing. Examination of the cells transduced by amplicons encoding GFP and human B7.1 suggested that the amplicons transduce a variety of cells, including professional antigen-presenting cells. From this and previous work, we conclude that amplicons may engender a potent immune response by directly transducing dendritic cells as well as by cross-priming of antigen produced by other transduced host cells.     

A model to identify direct costs of nursing education: the Colorado experience

During spring 2003, national, state, and local economic factors converged in a manner that propelled us to better identify the costs of the educational programs offered within the University of Colorado Health Sciences Center School of Nursing (SON). Two factors prompted analysis of direct costs of the nursing education programs: a shrinking state appropriation and a 36.7% rescission of state funds during that academic year. The SON supports 618 students in four programs (baccalaureate, master of science, doctor of nursing, and doctor of philosophy). During summer 2003, the SON leadership team met numerous times in an iterative process to clarify assumptions and make recommendations in an attempt to cost out academic programs. Data were obtained from a variety of sources. The SON Office of Budget and Finance provided revenue and expense data. The Office of Academic Affairs provided course schedules, the course offering plan, and projected student enrollment in courses. The Division Chairs provided data concerning faculty workload and faculty areas of expertise. The data were compiled in Access tables and arrayed in a series of Excel spreadsheets that captured course data and faculty data. A "what-if" analysis was completed to determine cost of a pilot accelerated baccalaureate program. This method provides a dynamic analytic system shown to be prospectively and retrospectively effective. As a result of this analysis, the following metrics are available: direct cost per student per course/program; revenue per student per course/program; faculty teaching FTE; and faculty-to-student ratio.     

The therapeutic relationship: dead or merely impeded by technology?

The ways in which current nurse education is delivered, combined with rapid increases in technological advances in health care, are having a major impact on the delivery of care to patients. This article focuses on one aspect of that care: the establishment, development and maintenance of the therapeutic relationship. The authors argue that the changes in education delivery and the rapid introduction of technologies are contributing to the possible demise of the contemporary nurse-patient relationship and, therefore, the loss of that essence of nursing which is essential to the patients' well-being and the nurses' professional satisfaction. The article explores the requisite knowledge and skills competences essential for the formation of the therapeutic relationship and asks whether these are being impeded by simulated educational activities and the advent of ubiquitous computing. The authors acknowledge the difficulties associated with the assessment of an effective therapeutic relationship and suggest a possible framework in which a performance of understanding of the formation of a therapeutic relationship can be established.     

Hepatic abscess: Sensitivity of imaging tests and clinical findings

The imaging studies of 63 patients with hepatic abscess were evaluated to determine the sensitivity of specific imaging tests and define causes of false-negative test results. Computed tomography (CT) detected 57 of 59 (97%) separate episodes of hepatic abscess. The two false-negative CT examinations were in patients with a diffuse low-density pattern throughout the liver. The radionuclide (RN) examination detected 16 of 20 (80%) cases, missing abscesses less than 2 cm in diameter. Ultrasound detected 33 of 42 (79%) cases, missing abscesses in the dome of the liver, small abscesses, and 2 large early abscesses. For all three imaging modalities, a specific diagnosis of abscess was possible only in those patients in whom CT scans demonstrated abscess gas (15%). The results of the imaging studies were correlated with the patients' clinical condition and laboratory findings. Thirty-one percent of patients were afebrile while 23% had normal white blood cell counts. Thirteen percent had totally normal liver function tests. We conclude that the clinical absence of fever, leukocytosis, or elevated liver function tests does not permit exclusion of the diagnosis of hepatic abscess. A CT scan is highly specific in excluding the diagnosis of hepatic abscess in the absence of diffuse liver disease. In this retrospective study CT was the most sensitive imaging modality available for the detection of hepatic abscess.     

Attitudes to back pain amongst musculoskeletal practitioners: a comparison of professional groups and practice settings using the ABS-mp

Chiropractors, osteopaths and physiotherapists play key roles in the management of low back pain (LBP) patients in the UK. We investigated the attitudes of these three professional groups to back pain using a recently developed and validated questionnaire, the Attitudes to Back Pain Scale for musculoskeletal practitioners (ABS-mp). A cross-sectional questionnaire survey was sent to 300 of each professional group (n=900). Responses were analysed from 465 practitioners: 132 chiropractors (28%), 159 osteopaths (34%) and 174 physiotherapists (37%). Overall, all three groups endorse a psychosocial approach to treatment, and see re-activation as a primary goal. However, physiotherapists and osteopaths tend to endorse attitudes towards limiting the number of treatment sessions offered to LBP patients more than chiropractors, and chiropractors endorse a more biomedical approach than physiotherapists. When practice setting (NHS versus private practice) was considered (in physiotherapists alone), physiotherapists working for the NHS endorsed limiting the number of treatment sessions more than those working in the private sector and would also less frequently advise their patients to restrict activities and be vigilant. The results may help explain current clinical practice patterns observed in these groups and their uptake of clinical guideline recommendations.     

The use of rapid sequence intubation by ambulance paramedics for patients with severe head injury

Objective: To determine the effects of rapid sequence intubation in patients with severe head injury performed by paramedics on a helicopter emergency medical service. Methods: The patient care records for patients with severe head injury who underwent rapid sequence intubation between November 1999 and February 2002 (inclusive) were examined. Data were extracted on the demographics of the patients, as well as the physiological changes before and after rapid sequence intubation. Results: There were 122 patients with severe head injury evaluated at the scene during the study period. Rapid sequence intubation was attempted in 110 patients and was successful in 107 (97%). Intubation was associated with improvements in systolic blood pressure, oxygen saturation and end‐tidal carbon dioxide levels, compared with baseline levels. Conclusion: Rapid sequence intubation in patients with severe head injury may be safely undertaken by helicopter‐based ambulance paramedics and is associated with improvements in oxygenation, ventilation and blood pressure. Further studies of this skill undertaken by road‐based paramedics are warranted.     

The effect of prestorage irradiation on posttransfusion red cell survival

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.