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V Gibson

Publications and source records attributed to V Gibson.

At least 19 recordsLinked to original sources
PubMed2001

Validity in action research: a discussion on theoretical and practice issues encountered whilst using observation to collect data.

AIM: The paper contributes to an understanding of validity in action research methodology by examining issues arising from our attempts to describe the role of an observer in an action research study. BACKGROUND: Our experiences in observing patient care in intensive care settings are used to illuminate discussion on the nature of validity in action research. CONTENT: The paper examines the nature of validity in action research methodology before briefly describing a study that included observing intensive care staff providing patient care. Various perspectives on observation as a research method are critically examined. These include observer role, level of participation, use of cover, structure and timing of observation. Validity in action research underpins the discussion in the paper. CONCLUSION: We conclude that it may not always be possible to categorize the role of the observer within existing definitions. It may be better to summarize the actual observer role as a way of illustrating validity so that the reader can judge the validity of the findings from an action research study.

Critical Care↗
PubMed2001

Land application of sewage sludge: perceptions of New Jersey vegetable farmers.

Understanding farmers' perceptions and choices regarding land application of sewage sludge is key to developing locally accepted strategies for managing its sewage sludge. Semi-structured interviews, with mostly open-ended questions were conducted with 50 fruit and vegetable farmers at the New Jersey Annual Vegetable Meeting in 1999. The in-depth interviews indicated that the application of sewage sludge to land is currently not a common agricultural practice for these growers. Perceived risks, including heavy metals in sewage sludge (soil-build up, crop-uptake), negative public perception, odour complaints, and increase of contaminants in the water supply outweigh economic incentives and soil improvement benefits. When naming benefits and drawbacks, farmers tend to think first of their crop and their land, and do not mention the environment. It is only when they are questioned directly about environmental benefits and risks that they discuss these aspects. Communication efforts should focus on practical information to which farmers can relate.

Adult↗
PubMed2000

Non-specific antiviral activity of antisense molecules targeted to the E1 region of human papillomavirus.

Antisense phosphorothioate oligonucleotides (ODN1 0x5 OMe) directed against the E1 start region of human papillomavirus 11 (HPV11) can inhibit papillomavirus induced growth of implanted human foreskin in a mouse xenograft model. Administration of a mismatch control oligonucleotide (ODN9 0x5 OMe), in which guanine was replaced with adenine in the same model, had no effect on papilloma induced growth. However, the apparent antiviral activity of ODN1 0x5 OMe was also shown in a lethal mouse cytomegalovirus (CMV) model, in which the oligonucleotides are not expected to have antisense activity. To understand the mechanisms of action of these oligonucleotides, a mismatch oligonucleotide (ODN61 0x5 OMe) was prepared which retained the CpG motifs of ODN1 0x5 OMe. This was tested in the mouse xenograft model and shown to have moderate inhibitory activity. As a definitive experiment, a comparison was made between the efficacy of the active oligonucleotide ODN1 0x5 OMe against two papilloma viruses HPV11 and HPV40. Both these viruses cause benign genital warts, but differ by four bases in their E1 sequence that was the target for ODN1 0x5 OMe. Papillomavirus induced growth in the mouse xenograft model was inhibited by ODN1 0x5 OMe in both cases, suggesting that oligonucleotide molecules have a non-specific antiviral activity that is not directly related to their antisense sequence.

Animals↗
PubMed1999

Artificial ventilation in the prone position.

Turning a ventilated patient into the prone position can greatly enhance arterial blood oxygenation independent of ventilator parameters. This article explores the physiology relating to pulmonary ventilation, highlighting an overall improvement in ventilation/perfusion matching as a result of the prone position. A series of small studies seems to suggest that prone positioning can have a dramatic effect on life-threatening hypoxia, including adult respiratory distress syndrome (ARDS) but as yet there have been no large, randomised, multi-centre trials to put beyond doubt the benefits of prone ventilation. Turning the patient prone precipitates many issues in caring for him/her in this position. Many are practical problems and the article goes on to explore a variety of these, including turning and positioning the patient, emergencies and access and the psychological effects of being in the prone position. It is important that nurses understand the physiological basis for any actions, including turning the patient prone, but it is also important that nurses doctors and other professionals appreciate the practical difficulties that this form of management can produce. All team members must work together to ensure a safe, cohesive approach to turning and caring for the ventilated patient in the prone position.

Adult↗
PubMed1996

Calcium buffering is required to maintain bone stiffness in saline solution.

This work determined whether mineral dissolution due to prolonged testing or storage of bone specimens in normal saline would alter their elastic modulus. In one experiment, small pieces of equine third metacarpal bone were soaked in normal saline supplemented with varying amounts of CaCl2. Changing Ca ion concentrations in the bath were monitored and the equilibrium concentration was determined. In a second experiment, the elastic moduli of twenty 4 x 10 x 100 mm equine third metacarpal beams were determined non-destructively in four-point bending. Half the beams were then soaked for 10 days in normal saline, and the other half in saline buffered to the bone mineral equilibrium point with Ca ions. Modulus measurements were repeated at 6 and 10 days. The equilibrium Ca ion concentration for bone specimens was found to be 57.5 mg l-1. The modulus of bone specimens soaked in normal saline significantly diminished 2.4%, whereas the modulus of those soaked in calcium-buffered saline did not change significantly.

Animals↗
PubMed1996

The factors influencing organ donation: a review of the research.

Transplantation of organs has become the treatment of choice for many conditions, yet there remains a worldwide shortage of donor organs. This paper reviews the factors which influence organ procurement. It concentrates on the public's and the professional's attitudes and examines the potential role research could play in overcoming these difficulties and thus increasing donor referrals.

Attitude of Health Personnel↗
PubMed1994

Does nurse turnover mean nurse wastage in intensive care units.

It has been claimed that the turnover rate of nurses working in Intensive Care Units (ICUs) is higher than in other areas of nursing; very little statistical evidence was found to support this claim. A questionnaire was designed to discover the reasons for nurse turnover among intensive care nurses. 45 nurses who had left the three ICUs of a large teaching hospital took part in the survey providing quantitative and qualitative data. High levels of dissatisfaction were found for career development, pay and clinical regrading, these being the main cause of turnover among the nurses who responded. Other causes were moving to another geographical area and the need for flexible hours. These findings can partly be explained by role conflict.

Adult↗
PubMed1993

Phase I trial of recombinant granulocyte-macrophage colony-stimulating factor in patients with lung cancer: clinical and immunologic effects.

Recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) may enhance the functional activity of monocytes and macrophages in vitro and in vivo and thereby have antitumor activity. A phase I trial using rhuGM-CSF was performed; the trial included 17 patients with unresectable and/or metastatic lung cancer. rhuGM-CSF was administered as a continuous infusion for 14 days at four dose levels: 60 micrograms/m2, 125 micrograms/m2, 250 micrograms/m2, and 500 micrograms/m2. Dose-limiting toxicity was pulmonary and occurred at 500 micrograms/m2, with the maximal tolerated dose (MTD) identified as 250 micrograms/m2. The hematologic effects of rhuGM-CSF included leukocytosis with significant correlations between dose level and the numbers of neutrophils, monocytes, eosinophils, and lymphocytes. Bronchoalveolar lavage was performed for 14 patients, and no effect on alveolar macrophage numbers was detected. Tumor biopsies were obtained in two patients, and no changes in macrophage infiltrates were detected with use of immunohistochemical studies. Serum levels of GM-CSF reached a steady state during week one and decreased or were undetectable during week two. No evidence of tumor regression was seen. rhuGM-CSF when administered as a continuous infusion was well tolerated and appears to modulate monocyte numbers and function in vivo.

Adult↗
PubMed1993

Phase I study of WR-2721 and carboplatin.

Because WR-2721 reduces the toxicity of cisplatin and carboplatin in preclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short relative to that of carboplatin, WR-2721 was administered in two divided doses. This schedule produced acceptable toxicity in 24 patients treated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In the subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopenia (platelets < 50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were similar to those reported for carboplatin alone. These results suggest that WR-2721 might increase the maximum tolerated dose of carboplatin from 400 to 500 mg/m2.

Adult↗
PubMed1992

A phase I trial of 5-fluorouracil, folinic acid, and alpha-2a-interferon in patients with metastatic colorectal carcinoma.

The mechanisms of biochemical modulation of 5-fluorouracil (5-FU) cytotoxicity by folinic acid (FA) have been elucidated, and the clinical use of this combination has improved response rates and survival in patients with metastatic colorectal cancer. Recently, Phase II trials also showed potential synergism between alpha-2a-interferon (rHuIFN-alpha 2a) and 5-FU. Therefore, a Phase I trial of these three agents 5-FU, FA, and rHuIFN-alpha 2a was conducted in patients with metastatic colorectal cancer. The drugs were given over 5 days, with dose escalation of either rHuIFN-alpha 2a or 5-FU. Fifty-five eligible patients were treated at eight dosing levels. The maximal tolerated dose (MTD) was as follows: 5-FU 430 mg/m2/d intravenously (IV) on days 1 to 5, FA 200 mg/m2 IV on days 1 to 5, and rHuIFN-alpha 2a 4.0 x 10(6) U/m2/d subcutaneously on days 1 to 5. The dose-limiting toxicities were mucositis and neutropenia. Objective responses were seen at most dosing levels, and overall 15 of 55 patients (27%; 95% confidence interval, 16% to 41%) responded (median duration, 6.5 months). A Phase II trial using the MTD is ongoing.

Adult↗
PubMed1992

Phase I trial of high-dose bolus interleukin-2 and interferon alfa-2a in patients with metastatic malignancy.

PURPOSE: Based on preclinical evidence that the antitumor effects of the combination of interleukin-2 (IL-2) and interferon alfa (IFN alpha) are greater than those of either cytokine alone, we have performed a phase I trial of recombinant IL-2 (rIL-2) and recombinant human IFN alpha 2a (rHuIFN alpha 2a) in patients with refractory malignancies. This study was an extension of an earlier trial that identified reversible myelosuppression as the dose-limiting toxicity of this combination. The present trial used modified definitions of unacceptable toxicity to allow exploration of higher doses of rIL-2. PATIENTS AND METHODS: Both rHuIFN alpha 2a 10.0 x 10(6) U/m2 intramuscularly (IM) and rIL-2 were administered three times weekly for 4 consecutive weeks. IL-2 was given by intravenous (IV) bolus injection at doses that were escalated in successive cohorts of four to six patients, provided that toxicity at the preceding dose level was acceptable. Unacceptable toxicity was defined as an elevation of the serum creatinine level to greater than 5 mg/dL, an elevation of the serum bilirubin level to greater than 5 mg/dL, dyspnea at rest, hypotension refractory to pressors, altered mental status, or other toxicities of grade 3 to 4, using the National Cancer Institute (NCI) Common Toxicity Criteria. The doses of rIL-2 administered were 4.0 x 10(6), 6.0 x 10(6), 8.0 x 10(6), 10.0 x 10(6), 12.0 x 10(6), 14.0 x 10(6), 18.0 x 10(6), 22.0 x 10(6), and 26.0 x 10(6) BRMP (Hoffman-LaRoche) U/m2. At a dose of rIL-2 10.0 x 10(6) BRMP U/m2, patients were also treated with doses of rHuIFN alpha 2a of 1.0 x 10(6) and 0.1 x 10(6) U/m2. RESULTS: A total of 57 patients were treated. Intolerable side effects (hypotension, pulmonary, and CNS toxicity) were produced by rIL-2 26.0 x 10(6) BRMP U/m2 and rHuIFN alpha 2a 10.0 x 10(6) U/m2. Two of 21 patients with renal cell carcinoma showed objective responses, and five of 17 patients with malignant melanoma responded. Two of these responses in melanoma were complete and continue to be longlasting. CONCLUSIONS: When given with rHuIFN alpha 2a 10.0 x 10(6) U/m2 as described above, the maximum-tolerated dose of rIL-2 is 22.0 x 10(6) BRMP U/m2. This dose of rIL-2 is equivalent to 50 to 60 MIU/m2, depending on the conversion factor used. Based on this experience and other trials, we favor phase II trials in renal cell carcinoma using an alternative dose schedule of this cytokine combination, in which rIL-2 is administered by continuous infusion. We suggest that phase II trials of this combination in patients with melanoma use an rIL-2 dose of 8.0 x 10(6) BRMP U/m2 by IV bolus injection three times weekly in combination with rHuIFN alpha 2a 10.0 x 10(6) U/m2 IM three times weekly.

Adult↗
PubMed1991

Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma.

A Phase I trial of tumor-infiltrating lymphocytes (TIL) expanded in vitro and administered on Days 1 and 8, with or without continuous infusion recombinant interleukin 2 (rIL-2) in 25 patients with metastatic renal cell carcinoma, was conducted. Eighteen of the 25 eligible patients were treated with TIL and escalating doses of rIL-2 (0.0, 3.0, 4.5 x 10(6) units/m2) on Days 1 to 5 and 8 to 12. Dose-limiting toxicity was pulmonary, and the maximum tolerated dose of rIL-2 was 3.0 x 10(6) units/m2. No clinical responses were observed. Immunological monitoring of peripheral blood lymphocytes demonstrated significant increases in CD3+ and CD56+ cells, including the activated T-cell subsets. Phenotypic analysis of cultured TILs demonstrated significant heterogeneity and the presence of CD3+CD4+ and CD3+CD8+ T-cells, with CD3-CD56+ and CD3+CD56+ populations also present. The majority of cultured TILs expressed HLA-DR and CD45RO, with a variable number expressing CD25. The rIL-2-expanded TILs possessed cytotoxicity against allogeneic and autologous tumor, with cytolytic activity against only autologous tumor seen in one patient. Results demonstrate that in vitro expansion of TILs is possible, but further studies are needed to define the biology of TILs in renal cancer and to isolate and expand tumor-specific T-cells.

Adult↗
PubMed1991

Phase I trial of natural human interferon beta in metastatic malignancy.

A phase I trial of natural human beta-interferon (nHuIFN-beta) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-beta was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 x 10(6) units/m2. Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P less than 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIFN-beta (P less than 0.01). Pharmacokinetic data demonstrated a short alpha half-life of 12.1 +/- 2.5 (SE) min and a beta half-life of 129.7 +/- 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-beta. In conclusion, toxicity of nHuIFN-beta given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-beta resemble those reported with rHuIFN-beta ser.

Adult↗
PubMed1991

Induction of cytokine messenger RNA and secretion in alveolar macrophages and blood monocytes from patients with lung cancer receiving granulocyte-macrophage colony-stimulating factor therapy.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the proliferation and differentiation of hematopoietic progenitor cells. Although preliminary data are available from clinical trials, the effect of GM-CSF on gene expression of immunocompetent cells in treated patients has not been studied. We previously demonstrated that in vitro treatment with GM-CSF also enhances maturation-related anti-tumor activities in mononuclear phagocytes. The purpose of the present study was to examine the effects of in vivo recombinant GM-CSF therapy on alveolar macrophages and blood monocytes, to determine if these cells demonstrated differential expression of cytokine genes, cytokine production, and tumoricidal activity. Alveolar macrophages and blood monocytes were isolated from 13 patients receiving a range of GM-CSF doses (60-250 micrograms/m2/day) by continuous infusion over a 2-week period. Both monocytes and macrophages were isolated prior to therapy and at day 10 of the infusion. Monocytes, in addition, were isolated on day 3 of infusion. Results indicated that GM-CSF therapy enhanced expression of tumor necrosis factor, interleukin 1, and interleukin 6 mRNA in both monocytes and alveolar macrophages. Differential responses, however, were observed in cytokine secretion; monocytes demonstrated enhanced secretion of all three cytokines by day 3 of treatment, but alveolar macrophages showed only enhanced interleukin 6 secretion at day 10. Monocyte tumoricidal activity after in vitro lipopolysaccharide stimulation was also significantly elevated by day 3 of treatment, but at day 10 activity was not statistically different from pretreatment values in either monocytes or alveolar macrophages. These data indicate that GM-CSF exerts striking time-dependent modulatory effects on gene expression and functional activities of monocytes and alveolar macrophages in vivo, although the responses of the two cell types differ with respect to cytokine secretion.

Gene Expression Regulation, Neoplastic↗
PubMed1991

Phase I trial of continuous infusion interleukin-2 and doxorubicin in patients with refractory malignancies.

A phase I trial was performed to assess the immunomodulatory activities, maximum tolerated doses, and the toxicity of recombinant interleukin-2 (rIL-2) administered in combination with doxorubicin to patients with refractory malignancies. Therapy was administered to successive cohorts of four to six patients who were treated at three different dose levels (1A, 1B, 2A). Levels 1-2 refer to doxorubicin (40 or 60 mg/m2) given as an intravenous (i.v.) bolus on day 1, and levels A-B refer to rIL-2 (1.0 or 3.0 x 10(6) U/m2) given as a continuous i.v. infusion on days 2-5, 9-12, and 16-19. Cycles were repeated every 28 days. Seventeen patients were entered in the trial. Dose limiting toxicity consisted of neutropenia, and the maximum tolerated dose (MTD) of the combination was doxorubicin 40 mg/m2 and rIL-2 3.0 x 10(6) U/m2. No objective responses were observed. Lymphocytosis related to rIL-2 occurred and flow cytometry demonstrated significant increases in the following subsets: CD3+CD25+HLADr+ and CD11b-CD16c+CD8-. Natural killer cell activity and lymphokine-activated killer (LAK) cell precursors were increased in patients treated at dose levels 1A and 1B (40 mg/m2 doxorubicin), but no consistent changes in LAK activity were noted. No clinical responses were seen and the overall toxicity of this combination was moderate to severe. Administration of doxorubicin prior to rIL-2 does not enhance the immunologic effects of rIL-2.

Adult↗
PubMed1990

Phase I trial of continuous infusion recombinant interleukin-2 and intermittent recombinant interferon-alpha 2a: clinical effects.

A phase I trial of high-dose continuous infusion rIL-2 over 5 days and i.m. recombinant human interferon-alpha (rHuIFN-alpha 2a) three times weekly in 23 patients with advanced malignancy has been completed. Cohorts of patients were treated at three different dose levels: rIL-2 3.0 x 10(6) u/m2 plus rHuIFN-alpha 2a either 5.0 or 10.0 x 10(6) u/m2, and rIL-2 4.5 x 10(6) u/m2 plus rHuIFN-alpha 2a 5.0 x 10(6) u/m2 over 4 weeks. Dose-limiting toxicity consisted of pulmonary and neurologic side effects, and the maximal tolerated dose was 3.0 x 10(6) u/m2 on days 1-5 or rIL-2, and 10.0 x 10(6) u/m2 three times weekly of rHuIFN-alpha 2a. Four partial responses (renal carcinoma, three; endometrial carcinoma, one) were seen. In conclusion, toxicity of this schedule of rIL-2 and rHuIFN-alpha 2a was significant, but manageable. Further investigation is needed to define the antitumor activity of this combination.

Adult↗
PubMed1990

Effects of heparin versus saline solution on intermittent infusion device irrigation.

The purpose of this study was to compare the effectiveness of 1 ml of 0.9% sodium chloride with 10 units of heparin in 1 ml sodium chloride solution, both containing benzyl alcohol, in maintaining patency and reducing the incidence of phlebitis in patients with intermittent infusion devices. The subjects (N = 32) were randomly assigned in a double-blind experimental design. Repeated-measures analysis of variance revealed no significant difference between the groups in phlebitis or patency variables. The results from this controlled study would suggest that 0.9% sodium chloride is as effective as 10 units of heparin in sodium chloride solution in maintaining intermittent infusion device patency and preventing phlebitis.

Adult↗